IndraLab

Statements

USP1 binds WDR48. 550 / 561
25 | 302 223
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"USP1 and UAF1 complex possesses potent deubiquitinase activity."
29138248
reach
"64 , 65 These agents inhibit the activity of USP1‐WDR48 complex in a non‐competitive manner."
32951278
sparser
"Interestingly, we note that not only USP1‐UAF1 is activated by DNA loading of PCNA, but also USP1 alone, which shows an increase in catalytic efficiency of from 2.3 mM −1  s −1 to 4.8 mM −1  s −1 ."
33619839
sparser
"USP1-UAF1 also acts on the mono-ubiquitinated form of the DNA polymerase processivity factor PCNA in translesion DNA synthesis (TLS) xref ."
31253762
biogrid
No evidence text available
28514442
reach
"This agreed with the native gel electrophoresis study suggesting that mutation of Ser313 of USP1 to Ala prevented formation of the USP1 and UAF1 complex, while the USP1 (S313D) mutant retains normal ability to form a complex with UAF1."
23116119
reach
"The formation of USP1 and UAF1 complex greatly stimulates the DUB activity of USP1."
23797609
sparser
"Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs."
22701671
reach
"UAF1 and the USP1 and UAF1 complex are also important in viral infection and pathogenesis, particularly in viral genomic integration and replication."
29091922
reach
"However, like UAF1, neither USP1 nor the UAF1 and USP1 complex exerts any influence on the D-loop reaction (XREF_SUPPLEMENTARY; data not shown)."
27239033
reach
"Here, we have used this assay to map the UAF1 binding motif in USP1, but such an assay can also be applied to evaluate the ability of different drug treatments to interfere with the formation of the USP1 and UAF1 complex (XREF_FIG)."
22701671
sparser
"For deubiquitination, USP1-UAF1 could efficiently remove ubiquitin from FANCD2- Ubi –FANCI, but not FANCD2- Ubi –FANCI- Ubi [ xref ]."
| PMC
reach
"This approach would greatly benefit from a knowledge of the three-dimensional structure of the USP1 and UAF1 complex, and from a clarification of the controversy regarding the USP1 region that mediates UAF1 binding [XREF_BIBR, XREF_BIBR]."
23937906
biogrid
No evidence text available
19075014
reach
"Consistent with this notion, USP1 was identified as a putative ATM and ATR substrate, and the interaction of USP1 and UAF1 with FANCI is regulated by DNA damage."
23813586
sparser
"The USP1–UAF1 complex can deubiquitinate several monoubiquitinated substrates, including human FANCD2-K561Ub ( hs FANCD2-Ub) ( xref ), human FANCI-K523Ub ( hs FANCI-Ub) ( xref ), and human PCNA-K164Ub (PCNA-Ub) ( xref )."
30456385
reach
"The USP1–UAF1 complex can deubiquitinate several monoubiquitinated substrates, including human FANCD2-K561Ub (hsFANCD2-Ub) (6), human FANCI-K523Ub (hsFANCI-Ub) (31), and human PCNA-K164Ub (PCNA-Ub) (25)."
30456385
reach
"Lastly, FANCD2 is deubiquitinated by USP1 and UAF1 complex to terminate the FA pathway."
33693881
sparser
"Based on these USP12 and USP46 structures, it is clear that UAF1 binds USP1 on the “finger” sub‐domain of the catalytic domain (Yin et al , xref )."
33619839
reach
"Since ML323 has an inhibitory effect on the UAF1/USP1 complex, its treatment keeps NLRP3 in check at the cellular level and prevents NLRP3 inflammasome activation."
| PMC
biogrid
No evidence text available
22701671
sparser
"Proteins involved in the formation of large protein complexes were also selected, such as UAF1, which is part of the deubiquitinating enzyme heterodimeric complex USP1-UAF1 [ xref ]; The Cyclin-Dependent Kinase 7 (CDK7), a subunit of the transcription/DNA repair factor TFIIH [ xref ], is both an effector kinase which phosphorylates both RNA Polymerase II and other transcription factors and a Cdk Activating Kinase (CAK) for essential CDKs [ xref ]; VPS26A, which is a subunit of the core ‘Retromer’ complex that mediates endosomal protein sorting and trafficking [ xref ]; and Munc18a and Munc18c, which regulate SNARE-complexes that mediate vesicle fusion [ xref ]."
33781758
reach
"The USP1 and UAF1 complex directly assembles on FANCI and its SIM domain for deubiquitination of both FANCI and FANCD2."
27543315
reach
"The FA ID complex is deubiquitinated by the UAF1 and USP1 complex."
30890612
sparser
"How di-monoubiquitination of ID2–DNA regulates the ability of USP1–UAF1 to remove ubiquitin from FANCD2 will be an interesting mechanism to investigate."
30456385
reach
"It suggests that ATAD5 UAF1del mutant protein has PCNA unloading activity even though it is defective in recruitment of the USP1 and UAF1 complex to PCNA-Ub to remove ubiquitin from PCNA."
23277426
sparser
"The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases."
33795880
reach
"The mixture was then assayed for DUB activity using Ub-AMC as a substrate, and the measured specific activity was compared to that of the copurified USP1 and UAF1 complex (treated as 100%)."
23116119
sparser
"ML323 binding to USP1-UAF1 also induced alterations in deuterium incorporation in the UAF1 subunit."
24531842
sparser
"For example, the CDK1mediated serine phosphorylation of USP1 disrupts the interaction between USP1 and UAF1."
35627217
reach
"USP1 and UAF1 complex enhanced TLR3/4 and RIG-I-induced IFN regulatory factor 3 (IRF3) activation and subsequent IFN-beta secretion."
29138248
reach
"We hypothesized that the USP1 NLSs could mediate the nuclear import of the USP1 and UAF1 complex."
22701671
sparser
"Our findings indicate that these NLSs mediate the nuclear localization of the USP1/UAF1 complex, supporting a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently relocates to the nucleus through active nuclear import mediated by USP1 NLSs."
22701671
sparser
"The cleavage rates show that the activity of a USP1 ΔNΔ1Δ2 –UAF1 complex is almost identical to that of USP1 FL –UAF1."
30456385
reach
"Our finding of the pSer313- dependent formation of USP1 and UAF1 complex points to a new approach of inhibiting USP1 activity."
23116119
sparser
"It was suggested that phosphorylation of USP1 at Ser313 serves as an interface for the association of USP1 with UAF1."
23116119
reach
"Furthermore, by genetically tagging UAF1 with a fluorescent protein, such as RFP, and using automated microscopy procedures, the assay can be readily adapted to a high throughput format in order to allow a high content screening for molecules that interfere with USP1 and UAF1 complex formation."
22701671
sparser
"Ubiqutination-linked phosphorylation of S559/S565 occurs predominantly downstream of monoubiquitination, and acts to inhibit FANCD2 de-ubiquitination by USP1-UAF1 and bypassed the need to deubiquitinate FANCD2 to achieve effective ICL repair [ xref ]."
| PMC
sparser
"It should be noted that USP1 forms a stable complex with UAF1, which stimulates the catalytic activity of USP1 [112]."
24239534
sparser
"However, isolated I Ub was completely deubiquitinated within 30 min by USP1‐UAF1 (Fig  xref D)."
32510829
reach
"Since only in vitro evidence for S313 phosphorylation regulated USP1 and UAF1 interaction has been provided, we decided to evaluate the role that this phosphorylation site may have in regulating USP1 binding to UAF1 in a cellular context."
25744535
reach
"To investigate the physiological function of USP1 and UAF1 complex in IRF3 activation, mouse peritoneal macrophages were transfected with UAF1 or USP1 siRNA."
29138248
reach
"Several studies have demonstrated that hELG1 specifically directs the USP1 and UAF1 complex to PCNA at the damage site and in doing so initiates the switch from the TLS polymerases to the replicative polymerases."
24958773
reach
"The USP1 and UAF1 complex is emerging as a novel target for cancer treatment, and inhibitors of USP1 catalytic activity have been reported to reverse the resistance to platinum based chemotherapeutic drugs in NSCLC cells [XREF_BIBR, XREF_BIBR] and to inhibit the growth of leukemic cell lines [XREF_BIBR]."
25744535
reach
"In this study, a high-throughput screening of nearly 10,000 bioactive small-molecules, followed by further validation and characterization of the best candidates, led to the identification of two potent and highly selective reversible inhibitors of the enzymatic activity of the USP1 and UAF1 complex, pimozide and GW7647."
23937906
reach
"If so, the Arg and N-end rule pathway acts, in this setting, as a regulator that determines the duration of DUB activity of the autocleaved Usp1 in the Usp1 and Uaf1 complex."
23159736
reach
"To our knowledge, these compounds are the first reported inhibitors against USP1-UAF1, and they demonstrate the feasibility of inhibiting the USP1 and UAF1 complex with small molecules."
24531842
sparser
"It will be important going forward to distinguish roles of UAF1-USP1 in regulating pSTAT1 relative to its role in the DNA damage response in HCMV infection."
36798153
reach
"UAF1 and USP1 knockdown both dramatically attenuated SeV- and ISD induced Tyr701 phosphorylation of STAT1, indicating the effect of USP1 and UAF1 complex is consistent for IFN-beta-mediated signaling (XREF_FIG)."
29138248
reach
"Furthermore, USP1, as a prototypical deubiquitylating enzyme, must bind with UAF1 for its catalytic action."
28659380
reach
"The Role of the Complex USP1 and WDR48 in Differentiation and Proliferation Processes in Cancer Stem Cells."
28302046
sparser
"Since only in vitro evidence for S313 phosphorylation-regulated USP1/UAF1 interaction has been provided, we decided to evaluate the role that this phosphorylation site may have in regulating USP1 binding to UAF1 in a cellular context."
25744535
sparser
"The interactions of USP1 and UAF1, an essential cofactor of USP1, with TonEBP were confirmed by coimmpunoprecipitation (coIP) ( xref E, xref C, and S1E)."
31376680
sparser
"The inhibition of the deubiquitinase complex USP1-UAF1 or the expression of constitutive fusion of ubiquitin to PCNA provides the missing clue required for DNA polymerase η recruitment and thereafter the introduction of A/T base pair (bp) mutations during the process of IgV gene diversification."
35432321
reach
"The USP1 and UAF1 complex is also recruited to mono-ubiquitylated PCNA via an interaction between UAF1 and the protein ELG1, a protein involved in replication complexes and in loading PCNA onto DNA for efficient replication, and independently identified as a factor required to suppress genomic instability [XREF_BIBR, XREF_BIBR]."
23712866
reach
"Last year, great strides were made in understanding the functional significance of ELG1 when it was discovered that the human homolog of ELG1 (which is also called ATAD5) not only interacts with PCNA and colocalizes with the sliding clamp at stalled replication forks with distinct foci structures in the nucleus, but also associates with the USP1 and UAF1 complex."
21640107
sparser
"Alternatively, FANCI ubiquitination may directly disrupt USP1‐UAF1 binding to FANCD2."
32510829
reach
"However, the exact structural details on how ML323 binds to the USP1/UAF1 complex remained elusive, which prevented further structure-based optimization of the inhibitor."
35625630
reach
"The exact mode of interaction between UAF1 and USP1 remains to be determined."
23797609
sparser
"When FANCD2- Ubi –FANCI- Ubi is dissociated from the DNA, USP1-UAF1 removes ubiquitin from FANCD2- Ubi –FANCI- Ubi [ xref ]."
| PMC
sparser
"On the other hand, UAF1 also binds USP1 to selectively remove the K48-linked polyubiquitylation of NLRP3, contributing to subsequent assembly and activation of NLRP3 inflammasome ."
34966378
reach
"Three Usp1 inhibitors explored this strategy, Pimozide [XREF_BIBR], ML323 [XREF_BIBR], [XREF_BIBR], [XREF_BIBR] and GW7647 [XREF_BIBR] each targeting the Usp1 and Uaf-1 complex in a non competitive manner."
25962961
sparser
"Finally, we found that in the full-length USP1–UAF1 context, a single point mutation in its N-terminus (R22E) is sufficient for specifically disrupting hs FANCD2-Ub deubiquitination but not hs FANCI-Ub or hs PCNA-Ub ( xref )."
30456385
reach
"A literature search regarding the role of the complex USP1 and WDR48 in inhibiting differentiation and increasing proliferation of CSC was performed, and possible selective molecule inhibitors of these deubiquitinase proteins were investigated."
28302046
reach
"To date, how USP1 and UAF1 interact and how the formation of the USP1 and UAF1 complex is regulated remains largely unknown."
23116119
sparser
"USP1 forms a complex with UAF1 in the cytoplasm, and then the complex translocates to the nucleus utilizing the two nuclear localization signals (NLSs) on USP1 ( xref )."
27060135
reach
"We carried out SEC-MALLS of the purified USP1 and UAF1 complex and the molecular weight obtained was approximately 220 KDa which closely corresponds to the 1:2 complex (235 KDa) rather than a 1:1 complex (160 KDa)."
27650958
reach
"USP1 by itself exhibits low DUB activity; however, this activity is significantly enhanced when bound as a USP1 and UAF1 complex."
24130053
sparser
"Given that human FANCI and FANCD2 share relatively low sequence identity with their Xenopus counterparts (~65% for FANCI and ~55% for FANCD2), it seems plausible that the requirement of DNA for efficient FANCD2 deubiquitination by human USP1-UAF1 becomes relaxed with the Xenopus protein."
31253762
sparser
"To determine the effect of inhibiting the UAF1-USP1 interaction on HPV11 RIs, 2D N/N AGE analysis of RIs generated from the WT genome in the presence of 20 µM ML323 was performed ( xref )."
30890612
reach
"USP1 interacts with the activating protein partner UAF1 (USP1 associated factor 1) and de-ubiquitylate Ubi-PCNA in the absence of DNA damage."
27379156
biogrid
No evidence text available
26388029
sparser
"USP1–UAF1, therefore, works to recycle and maintain appropriate levels of both monoubiquitinated and non-ubiquitinated FANCD2."
30456385
sparser
"Interestingly, the ubiquitin on FANCI was also protected from USP2, USP7 and USP1‐UAF1 deubiquitination in the I Ub D2 Ub ‐DNA complex."
32510829
sparser
"In that study xref , the human FA core complex was used to ubiquitinate the FancI-FancD2 complex from Xenopus laveis , and the modified Xenopus ID2 complex was then tested with human USP1-UAF1."
31253762
reach
"Deubiquitination of both FANCD2 and FANCI, which is also critical for ICL repair, is achieved by the USP1 and UAF1 complex."
34137174
sparser
"The association of USP1 and UAF1 in cells is likely regulated in response to DNA damage."
23797609
sparser
"Interestingly, the FANCD2 DUB activity of USP1-UAF1 that harbors a DNA binding defective UAF1 mutant is fully restored upon the incorporation of wild type but not a DNA binding defective form of RAD51AP1."
31253762
reach
"The finding that the non phosphorylatable S313A mutant version of USP1 binds and is stabilized by UAF1 in our cell based assays indicates that phosphorylation at S313 is not critical for USP1 and UAF1 complex formation in a cellular context."
25744535
sparser
"USP1-UAF1 complex increased TLR3/4 and RIG-I mediated IFN-β production, and the discovered USP1-UAF1 inhibitor ML323 can reduce interferon expression and promote viral replication both in vivo and in vitro ( xref )."
34966378
reach
"For example, WDR48 interacts with USP1, USP12 and USP46 to activate their DUB activity."
27880911
sparser
"To complete the pathway, ubiquitin must be removed by the USP1-UAF1 complex xref – xref ."
36050501
reach
"Since ATAD5 interacts with the USP1 and UAF1 complex and USP1has been reported to regulate centrosome duplication by increasing ID1 levels [XREF_BIBR, XREF_BIBR], we speculated that ATAD5 modulates ID1 to regulate centrosome duplication."
32594826
reach
"Here we show evidence that the USP1 and UAF1 complex has a FANCD2 independent function in promoting HR repair."
27463890
reach
"Disruption of USP1/UAF1 complex promote level of FANCD2/FANCI ubiquitination and DNA repair defects, suggesting a failure in the completion of FA pathway (Nijman et al., 2005b, Smogorzewska et al., 2007)."
27211605
reach
"Importantly, several inhibitors of the USP1 and UAF1 complex have been recently shown to act synergistically with cisplatin in cancer derived cell lines [XREF_BIBR, XREF_BIBR, XREF_BIBR], suggesting that this complex may represent a valid therapeutic target in cancer."
25744535
sparser
"On the other hand, UAF1 also binds USP1 to selectively remove the K48-linked polyubiquitylation of NLRP3, contributing to subsequent assembly and activation of NLRP3 inflammasome ( xref )."
34966378
sparser
"On the other hand, UAF1 also binds USP1 to selectively remove the K48-linked polyubiquitylation of NLRP3, contributing to subsequent assembly and activation of NLRP3 inflammasome (Song et al., 2020)."
34966378
reach
"Probing the interaction between UAF1 and the USP1 inserted domain (USP1_ID) by a pull-down experiment."
23116119
sparser
"Ubiquitinated FANCI/FANCD2 complex is finally deubiquitinated by ubiquitin specific peptidase 1-USP1-associated factor 1 (USP1-UAF1)."
32945661
reach
"However, to the best of our knowledge, only a few of them have, as yet, entered into clinical trials.Recently, a HTS approach led to the identification of two potent and selective reversible inhibitors of the enzymatic activity of the USP1/UAF1 complex, pimozide and GW7646."
| PMC
reach
"First, the UAF1 interacting region of USP1 identified here might be targeted to disrupt the USP1 and UAF1 interaction with therapeutic purposes."
22701671
sparser
"USP1 forms a complex with USP1-associated factor 1 (UAF1), which reduces K48-linked ubiquitination of TBK1 and stabilizes it, resulting in the downstream activation of IRF3 and promotion of IFN-β secretion."
35283827
sparser
"One explanation for FANCI's conjugated ubiquitin facilitating a USP1‐UAF1 resistant complex is that this ubiquitin interacts with FANCD2."
32510829
reach
"ML323, an inhibitor of the USP1/UAF1 complex, was developed by Zhuang Lab [80, 81] and stood to be the only USP family DUB inhibitor that met the chemical probe criteria [82] by 2016."
35625630
reach
"To determine whether this domain contributes to the interaction between USP1 and UAF1, a truncated USP1 (amino acids 235-408) (USP1_ID) with a N-terminal GST fusion was generated for pull-down assay with UAF1."
23116119
biogrid
No evidence text available
18082604
reach
"Human Elg1 and ATAD5 promotes PCNA deubiquitination by recruiting the USP1 and UAF1 complex to ubiquitinated PCNA."
23907118
sparser
"Moreover, it has been suggested that USP1‐UAF1 travels with elongating replication forks where it deubiquitinates its substrates."
33619839
sparser
"Previous work has shown that when DNA is removed from the reaction, di‐monoubiquitinated ID2 is no longer resistant to deubiquitination by USP1‐UAF1 xref , xref , but it is currently not clear how DNA may protect I Ub D2 Ub from USP1‐UAF1 deubiquitination."
32510829
reach
"Taken together, ELG1 specifically directs USP1 and UAF1 complex for PCNA deubiquitination."
20147293
reach
"Inhibiting the USP1 and UAF1 complex also compromises TLS by increasing levels of monoubiquitinated PCNA, another substrate of USP1, suggesting that inhibition of the USP1 and UAF1 complex can simultaneously target two major steps in the FA pathway."
26194820
reach
"On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1 and UAF1 complex."
22701671
reach
"Our findings indicate that these NLSs mediate the nuclear localization of the USP1 and UAF1 complex, supporting a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently relocates to the nucleus through active nuclear import mediated by USP1 NLSs."
22701671
sparser
"USP1‐UAF1 is known to play a role in PCNA‐Ub‐mediated translesion synthesis (Huang et al , xref )."
33619839
reach
"The inhibition of the deubiquitinase complex USP1-UAF1 or the expression of constitutive fusion of ubiquitin to PCNA provides the missing clue required for DNA polymerase η recruitment and thereafter the introduction of A/T base pair (bp) mutations during the process of IgV gene diversification."
35432321
sparser
"Here, we report the reconstitution of substrate deubiquitination by USP1–UAF1 that allows for a modular approach to understanding the molecular requirements for deubiquitination of physiological substrates."
30456385
sparser
"Taken together, these data establish that recombinant USP1–UAF1 is able to directly deubiquitinate diverse monoubiquitinated substrates in vitro without the need for auxiliary factors."
30456385
sparser
"Interestingly, and despite the presence of FANCI, which may also recruit the DUB complex ( xref ), USP1 ΔN –UAF1 and USP1 R22E –UAF1 are not able to fully deubiquitinate hs FANCD2-Ub, suggesting that any indirect recruitment of USP1–UAF1 by FANCI does not completely compensate for the loss of the USP1 N-terminus."
30456385
biogrid
No evidence text available
25744535
reach
"Chen et al. subjected the human USP1 and UAF1 complex to a quantitative high-throughput screening (hHTS) and defined potent and selective inhibitors of USP1 and UAF1."
29958636
sparser
"However, it was suggested recently that DNA shields ubiquitinated ID2 from the DUB activity of USP1-UAF1, such that the removal of DNA would lead to a marked enhancement of the efficiency of ID2 deubiquitination xref ."
31253762
sparser
"Efficient deubiquitination of FANCD2 occurred upon the addition of USP1-UAF1 (Fig.  xref )."
31253762
reach
"The cleavage rates show that the activity of a USP1 –UAF1 complex is almost identical to that of USP1 –UAF1."
30456385
reach
"We demonstrated using mass spectrometry that treatment of purified wild-type USP1 and UAF1 complex with PP1 effectively removed the phosphate group from Ser313 and Ser67."
23116119
reach
"In this study, we showed that the previously described interaction between the viral E1 helicase and the cellular UAF1 and USP1 complex is necessary for the completion of bidirectional replication and the subsequent initiation of the unidirectional replication mechanism."
30890612
reach
"The compound was found to be ‘largely reversible’, not binding at the active site and not acting via USP1/UAF1 complex disruption."
26852935
reach
"The second possibility is that ELG1 enhances or stabilizes the interaction between USP1 and its activating factor UAF1."
21640107
sparser
"For example, regarding FANCD2 ubiquitination, the extent of ID2 chromatin association or foci formation could be assessed in cells where FANCI cannot be ubiquitinated and USP1‐UAF1 is additionally defective."
32510829
sparser
"Our biochemical reconstitution studies (Fig.  xref and Supplementary Fig.  xref ) revealed that, via its DNA binding activity, RAD51AP1 targets the DNA binding defective USP1-UAF1 3A or USP1-UAF1 11A complex to deubiquitinate FANCD2 on DNA."
31253762
sparser
"Interestingly, the interaction of USP1 and UAF1 was not affected by H 2 O 2 , suggesting that the inhibition is likely caused by oxidation of the catalytic active site of USP1, which is consistent with other DUBs ( xref ; xref ; xref )."
34177595
sparser
"UAF1 has been regarded as the substrate recognition subunit of the USP1-UAF1 complex xref , xref ."
31253762
sparser
"We further demonstrate that ubiquitination of FANCI largely protects the ID2 complex from USP1‐UAF1 deubiquitination, which likely contributes to the maintenance of ubiquitination‐associated ID2‐DNA binding enhancement in the cellular context."
32510829
reach
"UAF1 SLD2 binds directly to a SIM in FANCI, bridging the interaction between USP1 and UAF1 and FANCD2 and FANCI."
26927199
sparser
"Interestingly, although the modifications in each pathway are assembled by distinct enzymes, they are removed by the same deubiquitinase (DUB), the USP1–USP1-associated factor 1 (UAF1) complex ( xref , xref , xref )."
30456385
sparser
"Hence, if such a complex results from USP1‐UAF1 deubiquitination, it is likely to retain a certain extent of the strong association with DNA observed with I Ub D2 Ub , potentially via partially stabilizing the closed state."
32510829
sparser
"Removal of FANCD2 from stalled replication forks is regulated by the deubiquitinating enzyme USP1-UAF1 and is necessary following repair to allow for replication restart xref ."
31240132
reach
"Both USP12 and USP46 were found to individually associate with all 3 WD40 proteins and both phosphatases, while USP1 associated with WDR48 and PHLPP but not WDR20, DMWD, or PHLPPL."
19615732
reach
"Mutational analysis suggests the same is true of WDR48 interaction and activation of USP1 (140)."
34391779
reach
"The tri phosphorylation of FANCI also inhibits the deubiquitinase activity of the USP1 and UAF1 complex over the ID2 complex until ICL repair and replication are completed [XREF_BIBR]."
| PMC
sparser
"Moreover, we confirmed the interaction of USP1‐WDR48 in HCC cells using co‐immunoprecipitation."
32951278
reach
"Our results indicate that the USP1 and UAF1 complex promotes HR, at least in part by suppressing NHEJ."
21482670
reach
"USP1 associates with UAF1 (USP1 associated factor 1), resulting in the heterodimeric USP1 and UAF1 complex that is required for deubiquitinase activity."
25229643
sparser
"One possibility is that in the absence of DNA ubiquitinated FANCD2 dissociates from ubiquitinated FANCI, and in isolation both proteins are known to be susceptible to USP1‐UAF1 activity xref ."
32510829
reach
"These three clones showed similar sensitivities to chemical cross linking agents, to a topoisomerase poison, camptothecin, and to an inhibitor of poly (ADP-ribose) polymerase (PARP), indicating that the USP1 and UAF1 complex is a regulator of the cellular response to DNA damage."
21482670
reach
"While the UAF1-USP12 and UAF1-USP46 complexes regulate histone deubiquitination and the cell survival- and growth promoting Akt pathway, the UAF1 and USP1 complex is involved in the Fanconi anemia (FA) DNA repair pathway."
30890612
reach
"However, not much has been studied regarding the roles of the USP1 and UAF1 complex in centrosome regulation."
32594826
reach
"Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1 and UAF1 complex."
27463890
reach
"The m 6 A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes, and further stabilized by the USP1/UAF1 complex after SCI."
36653190
reach
"Deubiquitination of FANCD2 and FANCI proteins by the multisubunit protein complex USP1 and UAF1 is required for the completion of the FA pathway."
28666371
reach
"Indeed, several inhibitors of the USP1 and UAF1 complex have been developed to target the FA pathway."
26194820
reach
"We found that Ser313 phosphorylation plays an essential role in regulating the formation of the USP1 and UAF1 complex."
23116119
sparser
"USP1 associates with its activating factor UAF1, and the USP1-UAF1 complex removes monoubiquitin from FANCD2 to complete the repair ( xref ) ( xref )."
26194820
reach
"By recruiting the UAF1 and USP1 complex to HPV replication forks, HPV11 may promote the deubiquitination of FANCD2 bound to viral genomes, thus promoting the engagement of BLM over the FA effector proteins."
30890612
sparser
"To examine whether FANCI deubiquitination activity by USP1:UAF1 is regulated by the 3SQ cluster, we performed in vitro deubiquitination reactions where xFANCI Ub :xFANCD2 Ub was treated with lambda phosphatase after ubiquitination."
32117957
reach
"There is evidence that USP1 and WDR48 complex promotes stem cell conservation and regulation of DNA damage repair."
28302046
reach
"The USP1 and UAF1 complex is required for regulation of the Fanconi anaemia (FA) DNA repair pathway."
29386062
reach
"Unlike the USP1 and UAF1 complex, USP1 (S313A) exhibited a catalytic efficiency (k cat / K m = 4.8 x 10 3 M -1 s -1) similar to that of the wild-type and USP1 (S313D) (XREF_TABLE)."
23116119
sparser
"USP1 (ubiquitin-specific peptidase 1), which promotes de-ubiquitination of mono-ubiquitinated PCNA [57] , forms a stable complex with UAF1 (USP1-associated factor 1), which stabilizes and activates U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28666590
sparser
"Replication stress and cell cytotoxicity caused by treatment with USP1-UAF1 inhibitor ML323 can be further sensitized by SPRTN loss."
35365626
sparser
"Surprisingly, and in direct contradiction with the recently published report xref , we find that the deubiquitination of FANCD2 by USP1-UAF1 requires DNA being present."
31253762
sparser
"To search for the domains of NLRP3 responsible for the interaction with USP1 and UAF1, a series of Myc-tagged NLRP3 truncated mutants were constructed (Fig.  xref )."
33247121
sparser
"With the substrates purified ( xref ), we assessed whether hs FANCD2-Ub, hs FANCI-Ub, or hs PCNA-Ub is directly deubiquitinated by USP1–UAF1 in vitro."
30456385
reach
"Furthermore, the USP1 and UAF1 complex can readily, and rapidly, de-ubiquitinate mono-ubiquitinated FANCD2 in an in vitro de-ubiquitination reaction [165]."
19101576
reach
"Further supporting this view, a recent report has shown that inhibiting the deubiquitinase activity of the USP1 and UAF1 complex sensitizes non small cell lung cancer cells to DNA damaging agents XREF_BIBR."
22701671
reach
"We find that UAF1 can bind the minimal USP1 catalytic domain (USP1 ) by size exclusion chromatography (SEC) (Fig 1D) and stimulate DUB activity on a fluorescent ubiquitinated-dipeptide substrate, Ub-KG (Fig 1E)."
30456385
sparser
"FANCI recruits the deubiquitinating enzyme USP1:UAF1 ( xref ), which prevents trapping of monoubiquitinated FANCD2 at non-productive DNA damage sites, but only ID2 Ub and not I Ub D2 Ub is a substrate ( xref )."
32167469
reach
"142 Liang et al. 143 investigated the binding effects of inhibitor ML323 on the human deubiquitinase complex USP1 and UAF1 using HDX MS and showed four moderately protected and two strongly protected peptides located outside the USP1 catalytic site, supporting the idea that ML323 is an allosteric inhibitor of USP1-UAF1."
25398026
reach
"It is important to note that none of these mutations disrupted USP1 and UAF1 interaction, according to the results of a nuclear relocation assay (Additional file 5B)."
25744535
reach
"The pSer313 dependent formation of the USP1 and UAF1 complex points to a new approach for inhibiting USP1 activity by disrupting the interaction between the UAF1 's WD40-repeat domain and the Ser313 containing phosphopeptide in USP1."
23116119
reach
"We assayed interaction with hsFANCD2 and found that a USP1 –UAF1 complex can capture the non-ubiquitinated substrate (Fig S7A)."
30456385
reach
"Human ELG1 (which is also called ATAD5) interacts with PCNA, colocalizes with the sliding clamp at stalled replication forks, and also associates with the USP1 and UAF1 complex which removes ubiquitin moieties from PCNA [XREF_BIBR]."
23195997
reach
"This observation suggests that the USP1 and UAF1 complex may be an important novel target in cancer treatment and thus, interfering with the formation and/or inducing the dissociation of the complex may represent a potential therapeutic strategy."
22701671
reach
"We next confirmed the ability of C527 to inhibit the USP1 and UAF1 complex in a dose dependent and time dependent manner, using Ub-AMC as a substrate (XREF_FIG)."
24130053
reach
"Hence, we hypothesized that the USP1‐WDR48 complex played critical roles in HCC by stabilizing the activity of their substrates."
32951278
reach
"On one hand, the UAF1 interacting region of USP1 identified here might potentially be targeted to disrupt the USP1 and UAF1 interaction with therapeutic purposes."
22701671
sparser
"Overall, our data provide molecular details of USP1-UAF1 regulation and substrate recognition."
33795880
sparser
"For example, USP1 interaction with UAF1 is necessary for DUB activity in vitro and deubiquitination of cellular substrates PCNA and FANCD2 ( xref ; xref ; xref )."
24075985
biogrid
No evidence text available
25744535
sparser
"The complex of USP1 and UAF1 (USP1-associated factor 1) removes the K48-linked ubiquitin chain after binding to TBK1."
34966378
reach
"ML323, a selective USP1-UAF1 inhibitor, was used to inhibit deubiquitinase activity of USP1 and UAF1 complex."
29138248
biogrid
No evidence text available
24850727
reach
"These results indicate that the two USP1 NLSs identified here mediate the import of the USP1 and UAF1 complex into the nucleus."
22701671
reach
"Our results do not definitely exclude the possibility that S313 phosphorylation may modulate the activity of the USP1 and UAF1 complex."
25744535
biogrid
No evidence text available
18082604
reach
"Importantly, the striking change in the nucleocytoplasmic localization of Xpress-UAF1 that results from GFP-USP1 co-expression provides the basis for a relocation assay to test USP1 and UAF1 complex formation in cells."
22701671
reach
"An S313D phosphomimetic mutation in USP1 can substitute for Ser313 phosphorylation in promoting the formation of the USP1 and UAF1 complex."
23116119
reach
"However, the IC 50 of C527 for these DUB enzymes was higher in comparison to USP1 and UAF1 complex (XREF_TABLE)."
24130053
biogrid
No evidence text available
19075014
reach
"A phosphomimetic USP1 (S313D) mutant can substitute Ser313 phosphorylation in promoting formation of the USP1 and UAF1 complex."
23116119
biogrid
No evidence text available
19075014
reach
"HSCARG enhances the interaction between PCNA and the deubiquitinase complex USP1 and UAF1 and inhibits the monoubiquitination of PCNA, thereby impairing the recruitment of Y family polymerases and increasing cell sensitivity to stimuli that trigger replication fork blockades."
31796584
sparser
"To examine to what extent the presence of I or I Ub influences D2 Ub deubiquitination, we compared the progress of D2 Ub , ID2 Ub and I Ub D2 Ub deubiquitination by USP1‐UAF1 (in the presence of dsDNA) in a time course (Fig  xref A)."
32510829
reach
"For example, USP1, USP12 and USP46 can interact with WD40-repeat protein USP1 associated factor 1 (UAF1), and UAF1 stimulates the catalytic activity of human USP1 through the formation of a tight complex [XREF_BIBR]."
29386062
reach
"UAF1 binds and stabilizes a non phosphorylatable S313A mutant version of USP1 in cell based assays."
25744535
reach
"As the USP1 and UAF1 complex is involved in TLS, pimozide and GW7647 may operate by limiting the ability of cancer cells to bypass CDDP induced DNA lesions."
24874729
sparser
"For example, we and others have shown that di-monoubiquitinated DNA-bound ID2 complexes remain resistant to deubiquitination ( xref ), suggesting that FANCD2-Ub and FANCI-Ub in the presence of DNA reciprocally regulate their deubiquitination by USP1–UAF1."
30456385
sparser
"A cryo-EM reconstruction of USP1-UAF1 in complex with monoubiquitinated FANCI-FANCD2 highlights a highly orchestrated deubiquitination process, with USP1-UAF1 driving conformational changes in the substrate."
33795880
reach
"The results presented in this paper also revealed clues as to how the interaction between E1 and the UAF1 and USP1 complex might lead to the BLM mediated initiation of unidirectional replication."
30890612
reach
"Interactions between USP1 and WDR 48 were confirmed using co-immunoprecipitation."
32951278
sparser
"UAF1 and USP1 form a deubiquitinase complex, which participates in a variety of biological processes, such as regulation of DNA repair processes and tumor pathogenesis."
29138248
reach
"hELG1 's role in PCNA de-ubiquitination is mediated by its interaction with the USP1 and UAF1 complex, which has been shown to work in de-ubiquitination [95]."
25795125
reach
"Thus, human Elg1 regulates PCNA deubiquitination by recruiting the USP1 and UAF1 complex to ubiquitinated PCNA on chromatin."
28134787
sparser
"A recent report suggests that xl FANCI is required for human USP1–UAF1 to remove ubiquitin from xl FANCD2-Ub ( xref )."
30456385
reach
"As shown in XREF_SUPPLEMENTARY, the steady-state kinetic constants of the USP1 (S42A)/UAF1, USP1 (S42D)/UAF1, USP1 (S67A)/UAF1, USP1 (S67D)/UAF1, and USP1 (S313D)/UAF1 complexes are close to that of the wild-type USP1 and UAF1 complex."
23116119
reach
"These results, collectively with our observation that SIVA1 depletion did not affect the chromatin association of USP1 and UAF1 (XREF_FIG), exclude the possibility that SIVA1 may act as an antagonist of PCNA deubiquitination by the USP1 and UAF1 complex."
24958773
sparser
"To test the DUB activity of USP1-UAF1, we first depleted the ATP content (to prevent further FANCD2 ubiquitination) of the above reaction by apyrase treatment."
31253762
reach
"hELG1 was found in association with the USP1 and UAF1 complex and down regulates PCNA mono-ubiquitination."
25795125
biogrid
No evidence text available
27463890
sparser
"This could be achieved in a cellular context by extraction of ubiquitinated ID2 complexes by the DVC1‐p97 segregase xref and subsequent deubiquitination by USP1‐UAF1."
32510829
sparser
"We assayed interaction with hs FANCD2 and found that a USP1 Δ1Δ2 –UAF1 complex can capture the non-ubiquitinated substrate ( xref )."
30456385
reach
"We therefore utilized a purified USP1 and UAF1 complex and performed a high throughput screen to identify a USP1 inhibitors (XREF_FIG)."
24130053
reach
"In a control experiment, the USP1 and UAF1 complex treated with phosphatase buffer did not result in an appreciable decrease in the activity of USP1 and UAF1 complex."
23116119
reach
"The USP1 and UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair."
27463890
reach
"In marked contrast, a band corresponing the USP1 and UAF1 complex was absent for USP1 (S313A) and UAF1 complex in both the Commassie blue stained gel (XREF_FIG, panel A) and the Western blotting gels (XREF_FIG, panel B and C)."
23116119
reach
"The USP1 and UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires the PCNA binding protein hELG1."
21896657
reach
"Interestingly, UAF1 contains a tandem repeat of SUMO like domains at its C-terminus which bind to a SIM (SUMO Interacting Motif) on hELG1 allowing the recruitment of the USP1 and UAF1 complex to the u[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25795125
reach
"The pSer313 dependent formation of USP1 and UAF1 complex points to a new approach of inhibiting USP1 activity by disrupting the interaction between the UAF1 's WD40-repeat domain and the Ser313 containing phosphopeptide in USP1."
23116119
reach
"Therefore, our results outline a novel mechanism for the control of TBK1 activity and suggest USP1 and UAF1 complex as a potential target for the prevention of viral diseases."
29138248
reach
"To gain insight into the mechanism of the USP1 and UAF1 complex in HR, we inactivated the nonhomologous end joining (NHEJ) pathway in UAF1 deficient cells."
21482670
reach
"The rise in ubiquitin corresponds to a decrease in the abundance of the de and ubiquitinating complex USP1 and WDR48, which targets FANCD2."
26365379
sparser
"The effect of inhibiting the UAF1-USP1 interaction was very similar to that of inhibiting the E1-UAF1 interaction, confirming that the loss of USP1 activity is essential to the replication defect caused by abrogated UAF1 binding."
30890612
sparser
"Crystals of the apo- and ubiquitin-bound form of USP1-UAF1, in conjunction with cryo-EM reconstructions of the enzyme-substrate complex, revealed important details of the specificity and regulation of this reaction."
34950659
sparser
"The USP1-UAF1 complex directly assembles on FANCI and its SIM domain for deubiquitination of both FANCI and FANCD2."
27543315
sparser
"We tested each I Ub in DUB assays and found that only I Ub‐I44A was also deubiquitinated to the same extent as I Ub‐WT by USP1‐UAF1."
32510829
reach
"Equally important as PCNA ubiquitylation is PCNA deubiquitylation, which is carried out by the USP1 and UAF1 complex in conjunction with ELG1."
21640107
reach
"The deubiquitination is performed by the USP1 and UAF1 complex resulting in the release of the ID2 complex from the chromatin to complete the ICL repair cycle [XREF_BIBR]."
| PMC
sparser
"Yu et al reported that the USP1‐WDR48 complex stabilized TANK‐binding kinase 1 by moving its K48‐linked polyubiquitination, and this process could be attenuated using the inhibitor ML‐323. xref Intriguingly, we found that WDR48 was also overexpressed in HCC tissues compared with normal tissues and was associated with poor prognosis in patients."
32951278
sparser
"Our results are consistent with a model in which USP1 and UAF1 form a complex in the cytoplasm that is subsequently translocated to the nucleus through active nuclear import mediated by the two USP1 NLSs ( xref )."
22701671
sparser
"When the repair process is completed, the FANCD2 and FANCI complex is deubiquitylated and dissociated from the repaired ICL site by the USP1-UAF1 complex and is then released from the DNA [ xref ]."
33810518
reach
"A small molecule, C527 (heterocyclic tricyclic 1,4-dihydro-1,4-dioxo-1H-naphthalene) (XREF_FIG) was identified which inhibited the USP1 and UAF1 complex."
24130053
reach
"Phosphatase treatment of the USP1 and UAF1 complex inactivates the enzyme complex."
23116119
sparser
"Inhibition of USP1–UAF1 activity by the specific small molecule ML323 leads to an increased sensitivity to platinum-based compounds in resistant cells ( xref )."
30456385
reach
"The USP1 and UAF1 complex promotes homologous recombination and DNA cross-link repair via deubiquitylation of two critical DNA repair substrates : Fanconi anaemia protein (FANCD2) [XREF_BIBR] and proliferating cell nuclear antigen (PCNA) [XREF_BIBR, XREF_BIBR]."
28659380
sparser
"To validate our kinetic modelling, we performed EMSA‐based binding analysis for USP1 (±UAF1) on DNA which confirmed that USP1‐UAF1 has stronger binding compared to USP1 alone (Fig  xref )."
33619839
reach
"Indeed inhibition of the Usp1 and Uaf-1 complex sensitises cells to chemotherapy."
25962961
reach
"USP1 and UAF1 complex facilitates IFN-beta production."
29138248
sparser
"Moreover, mutagenesis of equivalent residues in the WDR48:USP1 system abrogates both USP1 binding to WDR48 and deubiquitination of a USP1 substrate in cells, suggesting that this interface, distinct f[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26388029
reach
"For example, WDR48 interacts with USP1, USP12, and USP46 to activate their DUB activity (Cohn et al., 2009; Yin et al., 2015)."
27880911
reach
"For high-throughput screening, we used the recombinant USP1 and UAF1 complex in a 4 muL assay volume to screen several libraries of 9,525 bioactive small molecules in qHTS mode, by testing each compound as a dilution series spanning the concentration range of 0.46 muM to 114 muM (see Experimental Procedures)."
22118673
reach
"UAF1 also binds and activates two other DUBs, USP12 and USP46 (19), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner (20, 21)."
30456385
reach
"This finding suggested that the USP1‐WDR48 complex played a tumour‐promoting role in HCC by stabilizing and deubiquitinating these hub genes."
32951278
reach
"These data altogether suggest that the USP1 and UAF1 complex promotes HR repair via multiple mechanisms : through FANCD2 deubiquitination, as well as by interacting with RAD51AP1."
27463890
reach
"In vitro, the USP1 and UAF1 complex can de-ubiquitinate mono-ubiquitinated PCNA more efficiently than USP1 alone [59]."
28666590
reach
"First, the protease complex USP1 and UAF1 deubiquitinates monoubiquitinated PCNA."
24657165
sparser
"Probing the interaction between UAF1 and the USP1 inserted domain (USP1_ID) by a pull-down experiment."
23116119
reach
"The UAF1 and USP1 complex plays a critical role in the FA DNA repair pathway, and it is possible that HPV11 RIs containing two converged theta replication forks are mistaken for ICLs and that the FA pathway is recruited to resolve the structures."
30890612
sparser
"USP1-813 UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses."
| DOI
sparser
"So far there is no structural information available for USP1 alone or the USP1‐UAF1 complex, but crystal structures of the paralogs with and without the activators have been solved (Yin et al , xref ; Li et al , xref ; Dharadhar et al , xref )."
33619839
sparser
"Lastly, FANCD2-Ub is downregulated by the USP1-UAF1 deubiquitinating enzyme complex, and the remaining adduct is removed via nucleotide excision repair (NER) to complete the ICL repair ( xref ; xref ) ( xref )."
31983075
reach
"These results provide new insights into the function and regulation of the USP1 and UAF1 complex."
26758085
sparser
"Since RAD51AP1, which stably associates with UAF1 xref , also possesses DNA binding activity xref , it was of considerable interest to test whether it would restore to USP1-UAF1 3A and USP1-UAF1 11A mutant complexes the ability to deubiquitinate FANCD2 on DNA."
31253762
reach
"It is, therefore, necessary to clarify these conflicting results, and to determine to what extent these two amino acid motifs, and the S313 phosphorylation site, contribute to USP1 and UAF1 interaction."
25744535
reach
"Of note, USP1 and UAF1 interactions demonstrated using this assay could be consistently validated by co-IP in the present study, as well as in our previous report [XREF_BIBR]."
25744535
reach
"Chemical cross linking of the USP1 and UAF1 complex."
23116119
sparser
"Once the USP1-UAF1 complex is formed, it translocates into the nucleus where the recruitment of FANCD2 and PCNA substrates using a SUMO-like domain takes a place to regulate DNA damage response [ xref ]."
32512887
reach
"Taken together, our data demonstrate the important regulatory role of the USP1 and UAF1 complex in HR repair through its regulation of the FANCD2-Ub and PCNA-Ub cellular pools."
24001775
reach
"Likewise, the SLD2 domain of UAF1 also binds to the SIM on hELG1 to direct USP1 and UAF1 binding to another important substrate, PCNA-Ub."
27148358
reach
"[237] ML323, a specific inhibitor of USP1 and UAF1 was found in the same study to enhance viral replication both in vitro and in vivo, thus adding evidence for the positive role of the USP1 and UAF1 complex."
33511009
reach
"Additionally, the same study disrupted the NHEJ pathway, via knockout of Ku70 (also known as XRCC6 or X-Ray repair cross complementing 6), in UAF1 -/-/- cells which restored the cellular resistance to camptothecin and the PARP inhibitor suggesting that the USP1 and UAF1 complex promotes HR, at least in part by suppressing NHEJ."
30831436
reach
"Their k cat and K m values are also similar to those of the corresponding doubly six-His-tagged USP1 and UAF1 complex (XREF_TABLE)."
23116119
reach
"XREF_BIBR, XREF_BIBR Human ATAD5 regulates PCNA deubiquitination by recruiting the USP1 and UAF1 complex to ubiquitinated PCNA."
23907118
sparser
"One substrate of the USP1-UAF1 complex is the monoubiquitinated FANCI-FANCD2 heterodimer, which is involved in the repair of DNA interstrand crosslinks via the Fanconi anemia pathway."
33795880
reach
"USP1 stably associates with UAF1 and WDR48, and its DUB activity and intracellular stability are dependent on the latter (Cohn et al., 2007; Villamil et al., 2012)."
27239033
sparser
"Further studies may reveal additional layers of specificity for substrates such as PCNA-Ub, which could also be mediated by the N-terminus of USP1–UAF1."
30456385
sparser
"USP1 associates with UAF1 (USP1-associated factor 1), resulting in the heterodimeric USP1/UAF1 complex that is required for deubiquitinase activity. xref The USP1/UAF1 complex has been shown to regulate the tolerance of DNA damage induced by DNA cross-linking agents through deubiquitination of PCNA (proliferating cell nuclear antigen) xref and FANCD2 (Fanconi anemia complementation group D2), xref which are proteins that function in translesion synthesis and the Fanconi anemia pathway, respectively."
25229643
sparser
"USP1–UAF1 directly deubiquitinates monomeric FANCD2-Ub and FANCI-Ub."
30456385
biogrid
No evidence text available
27463890
sparser
"However, the PYD domain mutant (PYD) lost the ability to bind USP1 and UAF1 (Fig.  xref )."
33247121
sparser
"FANCI ubiquitination protects ID2 Ub complex against USP1‐UAF1 deubiquitination."
32510829
sparser
"Recent studies corroborate that Ser313 is not critical for USP1:WDR48 binding and function ( Olazabal-Herrero et al., 2015 )."
26388029
reach
"Moreover, the USP1 and WDR48 complex was found to downregulate the polyubiquitination of TAK1 and mediate its in vitro stability."
33461373
sparser
"ID2 Ub -DNA, on the other hand, can be efficiently deubiquitinated by USP1-UAF1, unless further ubiquitination on FANCI occurs."
36385258
reach
"Therefore, our findings have shed a light on the novel role of the USP1 and WDR48 complex in promoting TGF-beta-induced EMT and migration in TNBC via in vitro stabilization of TAK1."
33461373
sparser
"The same effect of I44A and F4A on FANCD2 deubiquitination was observed when using four times lower concentrations of USP1‐UAF1 in single time‐point DUB assays (Fig  xref A)."
32510829
reach
"Besides inhibiting its enzymatic activity, an alternative approach to target USP1 could be interfering with the formation of the USP1 and UAF1 complex, which is not disrupted by pimozide and GW7647 [XREF_BIBR]."
23937906
sparser
"The second possibility is that ELG1 enhances or stabilizes the interaction between USP1 and its activating factor UAF1."
21640107
reach
"We then investigated the effects of USP1 and UAF1 complex on viral replication using a vesicular stomatitis virus (VSV, another kind of ssRNA virus recognized by RIG-I) infection model."
29138248
sparser
"Once the DSB is repaired, FANCD2-Ub has to be extracted from the lesion; for this to occur, it has to be deubiquitinated by the USP1-UAF1 deubiquitinase complex and p97."
| PMC
reach
"Therefore, we speculate that TBK1 may be a target of USP1 and UAF1 complex."
29138248
sparser
"These results suggest that USP1 Ser313 phosphorylation is required for formation of the complex between USP1 and UAF1."
23116119
reach
"USP1 and UAF1 complex facilitates IRF3 activation."
29138248
reach
"We have previously described a cellular relocation assay to evaluate USP1 and UAF1 interaction [XREF_BIBR]."
25744535
reach
"Among these ten genes, the high expression of seven genes was significantly related to poor OS (BPTF, SETD2, SMARCC1, UBXN7, SMC3, PBRM1 and SF3B1) (Figure 9C), while the other three genes showed no significance (ATRX, SIN3A and USP34) (Figure S3).3.8 Validation of the interaction between USP1 and WDR48 in HCC cell lines."
32951278
reach
"Setting up and exploring an Arg and N-end rule based in vitro ubiquitylation and degradation system, with the Usp1 and Uaf1 complex as its autocleaved substrate, is likely to be a particularly informative approach to mechanistic questions in this arena, and to some physiological questions as well."
23159736
reach
"Furthermore, the ectopic expression of ATAD5 mutant protein (ATAD5 UAF1del) that does not interact with the USP1 and UAF1 complex and results in defective PCNA deubiquitylation reduced chromatin bound PCNA level similar to the ectopic expression of wild-type ATAD5 (XREF_FIG)."
23277426
reach
"The USP1 and UAF1 complex has also been reported to participate in homologous recombination [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
32594826
sparser
"Notably, even though RAD51AP1 DM could associate with UAF1 and the UAF1 3A and UAF1 11A mutants just as avidly as its wild type counterpart (Supplementary Fig.  xref and ref. xref .), it failed to restore FANCD2 DUB activity to USP1-UAF1 3A (Fig.  xref , lanes 7 and 11)."
31253762
reach
"To further investigate whether USP1 and UAF1 complex could inhibit TBK1 protein degradation, a cycloheximide (CHX) chase experiment was performed."
29138248
sparser
"We find that FANCD2 ubiquitination enhances binding of the ID2 complex to dsDNA, while FANCI ubiquitination protects the complex from deubiquitination by USP1‐UAF1."
32510829
reach
"Reaching these nuclear substrates first requires nuclear import of the USP1 and UAF1 complex, which is mediated by two nuclear localization signals (NLSs) in USP1 [XREF_BIBR]."
23937906
reach
"After a 30 min treatment, 4% of the activity for the treated USP1 and UAF1 complex remain."
23116119
reach
"Mutation of Ser313 to Ala on USP1 abolished the complex formation between USP1 and UAF1, thus prevented the activation of USP1 by UAF1."
23797609
sparser
"Together with a recently reported specific and allosteric USP1-UAF1 small molecule inhibitor (Liang et al., 2014) , our studies suggest that blocking the allosteric activation pathway might be an alternative strategy for discovering USP inhibitors with high specificity."
27373336
reach
"Our native gel electrophoresis following the incubation of USP1 and UAF1 with pimozide or GW7647 (up to 10 x IC 50) showed no dissociation of the USP1 and UAF1 complex (XREF_SUPPLEMENTARY)."
22118673
sparser
"We also predict that a conformational change induced by phosphorylation of the S3Q cluster alters the association of the adjacent SLIM domain of FANCI with USP1:UAF1, as a mechanism for the observed reduction in USP1:UAF1 binding in S3Q phosphomimic proteins."
32117957
reach
"To further clarify the target of USP1 and UAF1 complex, we examined the association between USP1-UAF1 and several adaptors."
29138248
sparser
"By reconstituting FANCD2-Ub, FANCI-Ub, and PCNA-Ub deubiquitination by USP1–UAF1, we identified the minimal components required for deubiquitination and discovered a unique sequence within the N-terminus of USP1 critical for removing ubiquitin from FANCD2 ( xref )."
30456385
reach
"Studies show that the formation of the USP1/UAF1 complex greatly enhances the catalytic activity of USP1, but USP1 alone has a very low level of activity (Cohn et al., 2007; Villamil et al., 2012)."
30319415
reach
"In this study, we identified that the USP1 and WDR48 complex could effectively enhance TGF-beta-mediated EMT and migration of TNBC cells."
33461373
sparser
"BRCA1 recruitment in S/G2 is also regulated by USP1–UAF1, which antagonises K63-Ub chains that serve as recruiters for BRCA1."
31769469
reach
"The rise in ubiquitin corresponds to a decrease in the abundance of the de and ubiquitinating complex USP1 and WDR48, which targets FANCD2 (Nijman et al., 2005)."
26365379
reach
"The USP1 and UAF1 complex is an important player in two major DNA damage response pathways, i.e., translesion DNA synthesis and the Fanconi anemia pathway."
23116119
reach
"When USP1 and UAF1 complex was treated with PP1, a large decrease in its activity was observed."
23116119
sparser
"In this regard, phosphorylation at the S313 residue has been recently reported to be critical for USP1 activity and interaction with UAF1 in an in vitro setting [ xref ]."
25744535
reach
"This view has recently gained experimental support with the identification of two compounds that inhibit the activity of the USP1 and UAF1 complex, and reverse the resistance of NSCLC cells to cisplatin [XREF_BIBR], a DNA damaging drug commonly used in cancer chemotherapy."
23937906
reach
"In contrast, two other known USP1 serine phosphorylations (Ser42 and Ser67) are dispensable with respect to the activity of the USP1 and UAF1 complex."
23116119
reach
"To explain this phenomenon, it has been suggested that HU disrupts the interaction between USP1 and its activating partner protein UAF1 (USP1 associated factor 1) [XREF_BIBR, XREF_BIBR]."
21640107
sparser
"For the substrate, mechanistic insight might also come from a co-structure of USP1:UAF1 and FANCI–FANCD2 Ub , which would uncover how the important deubiquitination reaction is controlled."
32725171
sparser
"We find that UAF1 can bind the minimal USP1 catalytic domain (USP1 ΔNΔ1Δ2 ) by size exclusion chromatography (SEC) ( xref ) and stimulate DUB activity on a fluorescent ubiquitinated-dipeptide substrate, Ub-KG TAMRA ( xref )."
30456385
sparser
"USP1 interacts with WDR48 in MHCC97H and SK‐Hep‐1 cells."
32951278
sparser
"Importantly, the addition of RAD51AP1 to reactions containing either USP1-UAF1 3A or USP1-UAF1 11A led to robust FANCD2 deubiquitination (Fig.  xref , lanes 7 and 9; Supplementary Fig.  xref )."
31253762
sparser
"To confirm that the interaction between USP1 and UAF1 is mediated by USP1 Ser313 phosphorylation, six-His-tagged USP1 was coexpressed with untagged UAF1 in insect cells."
23116119
reach
"To test this possibility, we purified the UAF1 and USP1 complex under reducing conditions (XREF_FIG)."
23463011
reach
"Overall work by these groups has confirmed the druggability of the Usp1 and Uaf -1 complex and the advantages of complex targeting approach."
26462181
sparser
"Although this can occur when D2 Ub is in isolation or in complex with FANCI, di‐monoubiquitinated ID2 complexes (I Ub D2 Ub ) bound to DNA remain largely resistant to USP1‐UAF1 deubiquitination xref , xref ."
32510829
reach
"The biological functions of USP1 and UAF1 complex."
23797609
sparser
"Deubiquitination was more nuanced – USP1:UAF1 could efficiently remove ubiquitin from FANCD2- Ub -FANCI but not FANCD2- Ub -FANCI- Ub ."
32117957
reach
"USP1 associates with its activating factor UAF1, and the USP1 and UAF1 complex removes monoubiquitin from FANCD2 to complete the repair (XREF_FIG)."
26194820
reach
"Recent work showed that phosphorylation of USP1 by kinase CDK1 promotes the complex formation between USP1 and UAF1."
23797609
biogrid
No evidence text available
27463890
sparser
"Our findings revealed an intriguing mechanism of regulating USP1 activity that combines phosphorylation of a key serine residue in USP1 and the specific interaction of USP1 with a WD40-repeat protein UAF1."
23116119
reach
"The USP1 and UAF1 complex is an important de-ubiquitylase for the RSR that can remove ubiquitin from PCNA and the FANCD2/I complex."
30257459
sparser
"As shown in xref , the de-ubiquitination of R1285Q ID Ub by USP1-UAF1 is indeed significantly faster than the wild type ID Ub ."
32269332
reach
"In human cells, ATAD5, the ortholog of yeast Elg1 appears to have a somehow different role from its yeast counterpart as it interacts, at stalled replication forks, with the USP1 and UAF1 complex and facilitates USP1 mediated PCNA de-ubiquitylation."
27379156
reach
"ELG1 (enhanced level of genomic instability 1) interacts with the USP1 and UAF1 complex and supports USP1 mediated de-ubiquitination of PCNA [62]."
28666590
reach
"However, the potential role of USP1 and UAF1 complex in the immune system, especially in the innate antiviral immunity, remains unknown."
29138248
sparser
"Notably, ML323 did not disrupt the association of the USP1 and UAF1 subunits in the complex."
24531842
sparser
"It has been postulated that the USP1-UAF1 complex is associated with pathogenesis for schizophrenia."
25522158
reach
"USP1 NLSs Mediate Nuclear Import of the USP1 and UAF1 Complex."
22701671
reach
"Given that reversible phosphorylation is a common mechanism of regulating the activity of protein complex, we next asked the question whether dephosphorylation of USP1 can lead to inactivation of USP1 and UAF1 complex."
23116119
sparser
"However, USP1‐UAF1 is apparently able to circumvent any protection formed from a locked ID2 Ub ‐DNA complex."
32510829
sparser
"Here, we show with reconstituted biochemical systems, which we developed, that efficient FANCD2 deubiquitination by the USP1-UAF1 complex is dependent on DNA and DNA binding by UAF1."
31253762
reach
"Binding of hUAF1 stabilizes hUSP1 and promotes interaction with PCNA-Ub and FANCD2-Ub [XREF_BIBR], and the USP1 and UAF1 complex promotes DNA double-strand break repair via homologous recombination [XREF_BIBR]."
29091922
reach
"In this regard, a relocation based assay for USP1 and UAF1 binding, which could be used to screen for compounds that disrupt their interaction, has been recently described [XREF_BIBR]."
23937906
sparser
"According to our data, this may occur because FANCD2's ubiquitin is no longer sufficiently protected against USP1‐UAF1 deubiquitination."
32510829
sparser
"We defined an interaction between UL138, a pro-latency HCMV gene, and the host deubiquintase complex, UAF1-USP1."
36798153
sparser
"The experimental systems that we and others xref , xref have developed will be useful for answering mechanistic questions regarding the intracellular functions of the USP1-UAF1 and for establishing the biological impact of cancer-associated mutations in the USP1-UAF1-RAD51AP1 complex."
31253762
sparser
"These data suggest that USP1‐UAF1 may be capable of modulating the ID2 Ub ‐DNA complex in order to gain access to FANCD2's conjugated ubiquitin."
32510829
sparser
"Using phosphomimetic and phosphodead mutants of FANCI we show that S559 and S565 are particularly important for protecting the complex from the activity of the deubiquitinating enzyme USP1:UAF1."
32117957
sparser
"Recently, Lim et al. xref , reported that USP1 also possesses a DNA binding activity with specificity for forked DNA (i.e. Y-shaped DNA with a duplex arm) and provided evidence that DNA binding exerts a modest stimulation of the DUB activity of USP1-UAF1."
31253762
reach
"However, like UAF1, neither USP1 nor the UAF1 and USP1 complex exerts any influence on the D-loop reaction."
27239033
sparser
"Deubiquitination of both FANCD2 and FANCI, which is also critical for ICL repair, is achieved by the USP1-UAF1 complex."
34137174
biogrid
No evidence text available
19615732
reach
"The DUB activity of USP1 and UAF1 complex treated with PP1 was measured."
23116119
sparser
"Usp1 forms a heterodimeric complex with Uaf1 ( U sp1- a ssociated f actor 1 ) (Wdr48), a protein containing WD40-type repeats ( xref , xref ; xref )."
23159736
reach
"The activity of USP1 after treatment with CDK1 for 2 h showed approximately 40% specific activity relative to the copurified USP1 and UAF1 complex."
23116119
reach
"The USP1 and UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified."
25744535
reach
"When the repair process is completed, the FANCD2 and FANCI complex is deubiquitylated and dissociated from the repaired ICL site by the USP1 and UAF1 complex and is then released from the DNA [XREF_BIBR]."
33810518
reach
"Ser313 phosphorylation not only is required for the tight association between USP1 and UAF1 but also plays a role in relaying the long-range allostery induced by the binding of UAF1."
23116119
reach
"The DUB activity of autocleaved Usp1 can apparently be retained if the N-terminal fragment (denoted as Usp1 Nt) and Gln Usp1 Ct are held together within the cleaved Usp1 and Uaf1 complex."
23159736
reach
"The SLD2 sequence of UAF1 binds to a SIM on hELG1, thus targeting the USP1 and UAF1 complex to its PCNA-Ub substrate."
21896657
sparser
"USP1 interacts with the activating protein partner UAF1 (USP1-associated factor 1) and de-ubiquitylate Ubi-PCNA in the absence of DNA damage ( xref )."
27379156
reach
"We recently demonstrated that selective USP1 and UAF1 complex inhibitors identified through high-throughput screening sensitized non small cell lung cancer cells to killing by a DNA damaging agent cisplatin."
23116119
sparser
"We wish to define mechanistically how DNA may affect the efficiency of FANCD2 deubiquitination by USP1-UAF1, and have developed a reconstituted system of highly purified human proteins for this purpose."
31253762
reach
"The monoubiquitylation licensing of the ID complex is antagonized by the DUB complex USP1 and UAF1; however, it is currently unknown how PTMs regulate USP1 and UAF1 after DNA damage."
25557546
biogrid
No evidence text available
18082604
reach
"For example, USP1 interaction with UAF1 is necessary for DUB activity in vitro and deubiquitination of cellular substrates PCNA and FANCD2."
24075985
sparser
"At higher concentrations of USP1‐UAF1 (100 nM), we found that FANCD2 can be deubiquitinated, albeit at slower rate than D2 Ub and ID2 Ub , which are rapidly deubiquitinated in under 10 min (Fig  xref A; Right )."
32510829
reach
"We next examined the potential functions of USP1 and UAF1 complex in vivo using ML323."
29138248
reach
"USP1 stably associates with UAF1 and WDR48, and its DUB activity and intracellular stability are dependent on the latter."
27239033
sparser
"USP1 binds to DNA independently of UAF1 and is stimulated preferentially by DNA structures mimicking a replication fork."
30576655
reach
"However, mutation of this sequence to AARAA did not abrogate UAF1 interaction (data not shown), indicating that the VERIV motif is not essential for USP1 and UAF1 complex formation."
22701671
sparser
"The exact mode of interaction between UAF1 and USP1 remains to be determined."
23797609
sparser
"This model, however, seems difficult to reconcile with the finding that the carboxy-terminal region of USP1 is unable to interact with UAF1 [ xref ], and would require further experimental validation."
23937906
reach
"The USP1/UAF1 complex is also recruited to mono-ubiquitylated PCNA via an interaction between UAF1 and the protein ELG1, a protein involved in replication complexes and in loading PCNA onto DNA for efficient replication, and independently identified as a factor required to suppress genomic instability [68, 69]."
23712866
sparser
"Given data from recent publications showing that USP1-WDR48 complexes have DNA binding activity19,20 , we first considered the possibility that perhaps the USP1 mutations could be affecting USP1's recruitment to chromatin or the replication fork."
35365626
reach
"The USP1 and UAF1 complex deubiquitylates the Fanconi anemia protein FANCD2, which promotes homologous recombination (HR) and DNA cross-link repair."
26927199
reach
"Several studies showed that UAF1 forms a complex with USP1 and stimulates the deubiquitination activity of USP1 both in vitro and in vivo."
23797609
reach
"We also show that a metabolic stabilization of Gln Usp1 Ct, a change that prolongs DUB activity of the autocleaved Usp1 in the Usp1 and Uaf1 complex, makes cells hypersensitive to UV irradiation."
23159736
reach
"Since USP1 affects centrosome duplication and ATAD5 interacts with the USP1 and UAF1 complex [XREF_BIBR, XREF_BIBR], we hypothesized that ATAD5 plays a role in centrosome duplication."
32594826
reach
"Using high throughput screening, we identified a small molecule inhibitor of the USP1 and UAF1 complex."
24130053
biogrid
No evidence text available
18082604
sparser
"Since USP1‐UAF1 is a specific deubiquitinase (DUB) for FANCD2 xref , xref , we wanted to assess whether alternative DUBs, that lack FANCD2 specificity (i.e. target structurally diverse substrates), are also able to access the ubiquitin on FANCD2 when this is in complex with I or I Ub ."
32510829
reach
"These data indicate that USP1 and UAF1 complex targets molecules upstream of IRF3 to inhibit IFN-beta production."
29138248
reach
"The USP1 and UAF1 complex deubiquitinates the Fanconi anemia protein FANCD2, thereby promoting homologous recombination and DNA cross-link repair."
21896657
sparser
"We demonstrated that the binding of UAF1 to USP1 does not affect the binding of ubiquitin to USP1."
23797609
reach
"High-throughput screening of some nine and a half thousand bioactive compounds with the USP1/UAF1 complex using a Ub-Rho substrate by the Zhuang group identified several low μM hits [68]."
26852935
reach
"In this work we discovered potent, and cell-active inhibitors of the USP1 and UAF1 complex through quantitative high-throughput screening (qHTS)."
22118673
reach
"For example, the CDK1-mediated serine phosphorylation of USP1 disrupts the interaction between USP1 and UAF1."
35627217
sparser
"Recent structural studies of the factors involved in FA pathways, such as the FA core complex, the FANCI:FANCD2 heterodimer and the USP1-UAF1 DUB complex, are prime examples ( xref )."
34950659
sparser
"Previous work on UAF1-USP1 binding showed WD40 domain of UAF1 was sufficient to act as an adapter protein and activate the catalytic DUB activity of USP1, which on its own has very little intrinsic catalytic activity in-vitro xref ."
31685642
reach
"These data support models in which the Usp1 and UAF1 complex is indirectly recruited to PCNA-Ub."
22989887
sparser
"In fact, in the context of the I Ub D2 Ub ‐DNA complex, FANCI deubiquitination was far from complete at 40 min, even at the highest USP1‐UAF1 concentration used (Fig  xref )."
32510829
reach
"Compared to the siRNA approach, the small-molecule inhibitor allowed us to probe the cellular function of USP1 and UAF1 without perturbing the level of USP1 and UAF1 complex in human cells."
22118673
reach
"Disruption of the USP1 and UAF1 complex leads to DNA repair defects similar to those of mutants in the FA pathway."
23624835
reach
"We demonstrated that the binding of UAF1 to USP1 does not affect the binding of ubiquitin to USP1."
23797609
sparser
"We hypothesized that since FANCI ubiquitination does not further enhance ID2‐DNA binding, its primary role may be in protecting FANCD2's ubiquitin from USP1‐UAF1 activity."
32510829
sparser
"In cells, unloading of FANCD2 Ub –FANCI Ub may be instigated by DVC1-p97 [ xref ] but removal of DNA from the FANCD2 Ub –FANCI Ub complex in vitro is sufficient to again permit the activity of USP1:UAF1 on the complex [ xref , xref ] highlighting the critical role that DNA plays in stabilizing the structure of the heterodimer."
32725171
reach
"Taken together, these data demonstrate that SJB2-043 is an inhibitor of the native USP1 and UAF1 complex."
24130053
reach
"Herein, we review the regulation, catalysis, and inhibition of the USP1 and UAF1 complex."
23797609
sparser
"Moreover, we observed that FANCD2 was deubiquitinated by USP1‐UAF1 faster than FANCI in the I Ub D2 Ub complex (Fig  xref )."
32510829
reach
"As shown in XREF_FIG, three discrete bands corresponding to the USP1 and UAF1 complex and the individual UAF1 and USP1 proteins were detected in native gel electrophoresis and Coomassie blue staining."
23116119
sparser
"Furthermore, BRCA1-deficient cells expressing a truncated variant of USP1 deficient in DNA binding fail to deliver USP1-UAF1 to replication forks to act on the ubiquitinated form of the proliferating cell nuclear antigen (PCNA) and are, consequently, impaired for the ability to stabilize stressed DNA replication forks xref ."
31253762
sparser
"Structural basis of FANCD2 deubiquitination by USP1-UAF1."
33795880
sparser
"We also employed Ub-VS as activity probe xref to establish that neither benzonase nor DNase I affects the intrinsic DUB attribute of USP1-UAF1 (Supplementary Fig.  xref )."
31253762
sparser
"Moreover, hELG1 (enhanced level of genomic instability 1), an alternative subunit of the RFC clamp loader complex, specifically directs the USP1-UAF1 dimer to PCNA for de-ubiquitination [ xref ]."
30586904
sparser
"These data suggest that access to the ubiquitin on FANCD2 for USP1‐UAF1 is reduced when in complex with ubiquitinated FANCI and DNA."
32510829
reach
"Likewise, the activity of the deubiquitinating complex USP1 and UAF1 over FANCD2 keeps the FA pathway in check 104, 105."
29756349
reach
"Our results indicate that the S313 phosphorylation site is not critical for USP1 binding to UAF1 or for PCNA deubiquitination in a cellular environment."
25744535
sparser
"USP1 forms a complex with UAF1 where its WD40 domain binds and stimulates the ubiquitin protease activity of USP1 to counteract the monoubiquitination of the FANCD2-FANCI heterodimer [ xref ]."
30831436
reach
"One substrate of the USP1 and UAF1 complex is the monoubiquitinated FANCI and FANCD2 heterodimer, which is involved in the repair of DNA interstrand crosslinks via the Fanconi anemia pathway."
33795880
reach
"ATR may also regulate FANCD2 ubiquitylation by targeting the FANCD2 deubiquitination complex USP1 and UAF1."
23813586
sparser
"Ubiquitination of FANCI, on the other hand, largely protects the ubiquitin on FANCD2 from USP1‐UAF1 deubiquitination, with key hydrophobic residues of FANCI's ubiquitin being important for this protection."
32510829
reach
"For the wild-type USP1 and UAF1, a single band corresponding to the complex was detected with both antibodies (XREF_FIG, panel B and C), confirming the presence of both USP1 and UAF1 polypeptides in the native gel band assigned as USP1 and UAF1 complex."
23116119
sparser
"To test this possibility, we examined the ubiquitin protease activity of full length USP1 bound in a complex with UAF1, with or without DNA, using the ubiquitin-AMC release assay and the ubiquitin CHOP2-Reporter assay ( xref ) ( xref ; xref ; xref ; xref ; xref )."
30576655
sparser
"Furthermore, the USP1–UAF1 complex has been shown to play critical roles in homologous recombination ( xref )."
30456385
reach
"The USP1 and UAF1 complex keeps in check FANCD2 ubiquitination under normal conditions."
19686080
reach
"Given the structural similarity between these USP14 inhibitors and the USP1 inhibitor ML323 (12), it is tempting to speculate that this equally drug-like lead may bind into a similar region of the USP1/UAF1 complex.In June 2015, Genentech and Almac Discovery announced a collaboration on an undisclosed USP target, whereby Almac Discovery's small-molecule leads would provide the starting point for a two-year joint research programme."
26852935
reach
"In this study, we subjected the human USP1 and UAF1 complex to high-throughput screening and identified potent and selective inhibitors against USP1 and UAF1."
22118673
reach
"Moreover, H 2 O 2 treatment did not affect the association of Usp1 with UAF1 (XREF_FIG), suggesting that inhibition of USP1 by oxidative stress is not likely caused by ROS mediated disruption of the Usp1 and UAF1 complex."
23219552
reach
"The USP1 and UAF1 complex deubiquitylates FANCD2 and FANCI."
20807115
biogrid
No evidence text available
18082604
sparser
"To ask if UAF1 DNA-binding is relevant for ID2 deubiquitination, we examined the mutant USP1-UAF1 3A and USP1-UAF1 11A complexes (Supplementary Fig.  xref ) in FANCD2 deubiquitination."
31253762
reach
"The crucial role that UAF1 binding plays as regulator of USP1 deubiquitinating activity raises the possibility that interfering with the formation of the USP1 and UAF1 complex may constitute a useful therapeutic strategy."
22701671
sparser
"A recent report has showed that the di-monoubiquitinated frog ID2 complex (both FANCD2 and FANCI monoubiquitinated), generated in the presence of plasmid DNA, remains resistant to deubiquitination by a GST-tagged USP1–UAF1 complex and only the removal of DNA permits efficient DUB activity ( xref )."
30456385
reach
"Like PCNA, FANCD2 ubiquitination is reversed by the USP1 and UAF1 complex (Nijman et al., 2005a; Cohn et al., 2007)."
19217402
reach
"It has been postulated that the USP1 and UAF1 complex is associated with pathogenesis for schizophrenia."
25522158
sparser
"USP1-UAF1 complex increased TLR3/4 and RIG-I mediated IFN-β production, and the discovered USP1-UAF1 inhibitor ML323 can reduce interferon expression and promote viral replication both in vivo and in vitro (Yu et al., 2017)."
34966378
reach
"Moreover, mutagenesis of equivalent residues in the WDR48 : USP1 system abrogates both USP1 binding to WDR48 and deubiquitination of a USP1 substrate in cells, suggesting that this interface, distinct[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26388029
reach
"Moreover, WDR20 is specific for USP12 and it did not stimulate the DUB activity of the USP1 and UAF1 complex."
23797609
sparser
"At the same time, phosphorylation can promote the interaction of USP1 and its cofactor UAF1, whereas the binding of OTULIN to LUBAC is blocked by phosphorylation."
34177595
reach
"The UAF1 and USP1 complex deubiquitinates FANCD2 during execution of the Fanconi anemia DNA damage response pathway."
27239033
reach
"The USP1 and UAF1 complex is responsible for regulating DNA break repair pathways such as trans-lesion synthesis pathway, Fanconi anemia pathway and homologous recombination."
25972987
sparser
"Our results indicate that the S313 phosphorylation site is not critical for USP1 binding to UAF1 or for PCNA deubiquitination in a cellular environment."
25744535
reach
"The identification of the UAF1 binding domain in USP1 may be of clinical relevance in the light of the recent observation that interfering with the activity of the USP1 and UAF1 complex sensitizes non small cell lung cancer cells to DNA damaging agents XREF_BIBR."
22701671
biogrid
No evidence text available
20147293
sparser
"The USP1‐UAF1 complex specifically targets ubiquitinated FANCD2 for deubiquitination utilizing an N‐terminal module of USP1 xref ."
32510829
sparser
"Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay."
25744535
sparser
"Surprisingly, the motif on ATAD5 responsible for the binding to UAF1–USP1 was found to coincide with a SIM, and a corresponding SUMO-like domain was identified in the C-terminus of UAF1, which is resp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23688817
reach
"Interestingly, inhibition of Usp1, a close homologue of Usp12 has been shown to have promising results in lung cancer systems which was achieved by inhibiting the Usp1 and Uaf-1 complex [XREF_BIBR], [XREF_BIBR]."
25216524
sparser
"Furthermore, the mechanism for the removal of ubiquitin from FANCD2 was also clarified by cryo-EM and crystallography experiments with USP1-UAF1 ( xref )."
34950659
reach
"Inhibiting the function of the USP1 and UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target."
22701671
reach
"A recent report has showed that the di-monoubiquitinated frog ID2 complex (both FANCD2 and FANCI monoubiquitinated), generated in the presence of plasmid DNA, remains resistant to deubiquitination by a GST-tagged USP1–UAF1 complex and only the removal of DNA permits efficient DUB activity (32)."
30456385
sparser
"Upon completion of DNA repair, the ID2 complex is deubiquitinated by the USP1-UAF1 deubiquitinase complex xref ."
33051438
reach
"The hypersensitivity to both camptothecin and a PARP inhibitor suggests that the USP1 and UAF1 complex promotes homologous recombination (HR)-mediated double-strand break (DSB) repair."
21482670
reach
"The USP1 and UAF1 complex promotes double-strand break repair through homologous recombination."
21482670
sparser
"The I36A mutation resulted in partial loss, whereas the F4A and L73A mutations on ubiquitin resulted in complete loss of USP1‐UAF1 activity (Fig  xref D)."
32510829
sparser
"Interestingly, whereas, as expected xref , xref , xref , UAF1 deficient cells showed an elevated level of monoubiquitinated FANCD2, but cells expressing either the UAF1 3A or UAF1 11A mutant harbored mostly deubiquitinated FANCD2 (Fig.  xref ), indicating that the UAF1 mutations have little or no impact on the FANCD2-specific DUB activity of the USP1-UAF1 complex in cells."
31253762
reach
"ML323, a selective small-molecule inhibitor of the UAF1 and USP1 complex, was used to test the requirement for USP1 activity in the replication of the HPV11 WT and VE mutant genomes."
30890612
reach
"The only currently accepted negative regulator of TLS is the deubiquitinase complex USP1 and UAF1."
23723248
sparser
"The tri-phosphorylation of FANCI also inhibits the deubiquitinase activity of the USP1-UAF1 complex over the ID2 complex until ICL repair and replication are completed [ xref ]."
| PMC
reach
"For USP1 (S313D) and UAF1 complex, a band similar to that of the wild-type USP1 and UAF1 complex was detected."
23116119
sparser
"Binding of USP1 by WDR48 was sensitive to deletions within the WD-repeats, indicating the importance of a presumed propeller domain ( Cohn et al., 2007 )."
26388029
sparser
"Moreover, the USP1-WDR48 complex was found to downregulate the polyubiquitination of TAK1 and mediate its in vitro stability."
33461373
reach
"As K48-linked ubiquitination is linked with protein degradation, the UAF1/USP1 complex stabilizes the degradation of NLRP3, which increases cellular NLRP3 levels and promotes NLRP3 inflammasome activation."
| PMC
sparser
"Several studies showed that UAF1 forms a complex with USP1 and stimulates the deubiquitination activity of USP1 both in vitro and in vivo ( xref , xref - xref )."
23797609
sparser
"The ATR phosphorylation sites are located in a flexible region of FANCI, adjacent to the FANCI ubiquitination site, and the FA core complex, Ube2T and USP1-UAF1 binding sites ( xref ), referred to here as the “phospho-loop” xref , xref , xref , xref ."
36050501
sparser
"The deubiquitination is performed by the USP1-UAF1 complex resulting in the release of the ID2 complex from the chromatin to complete the ICL repair cycle [ xref ]."
| PMC
biogrid
No evidence text available
22701671
sparser
"ML323 is a highly effective inhibitor of USP1-UAF1 deubiquitinase complex, blocking the allosteric activation pathway may be another strategy to study and discover USP inhibitors [ xref , xref , xref ]."
33498168
sparser
"Wild type and mutant forms of RAD51AP1, the ID2 complex, and the USP1-UAF1 complex were expressed and purified as described xref , xref , xref , xref (Supplementary Fig.  xref )."
31253762
reach
"Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1 and UAF1 complex."
22701671
reach
"To identify the influence of the complex USP1 and WDR48 during the CSC tumorigenesis process, and whether this complex is a possible therapeutic target."
28302046
reach
"Taken together, C527 is a pan deubiquitinating enzyme inhibitor in vitro, with a high nanomolar IC 50 for the USP1 and UAF1 complex."
24130053
reach
"Yu et al reported that the USP1‐WDR48 complex stabilized TANK‐binding kinase 1 by moving its K48‐linked polyubiquitination, and this process could be attenuated using the inhibitor ML‐323."
32951278
reach
"For instance, the USP1 and UAF1 complex deubiquitinates the cellular monoubiquitinated substrates Ub-FANCD2 and Ub-PCNA."
24130053
sparser
"H 2 O 2 does not affect the interaction of USP1 with UAF1 ( xref ), suggesting that the inhibition is likely caused by oxidation of USP1 active site."
23463011
reach
"USP1 forms a complex with UAF1 in the cytoplasm, and then the complex translocates to the nucleus utilizing the two nuclear localization signals (NLSs) on USP1."
27060135
sparser
"Recent studies have even suggested that USP1 has DNA-binding activity and that USP1-WDR48 complexes localize to stalled replication forks 19, 20 ."
35365626
sparser
"UAF1 also binds and activates two other DUBs, USP12 and USP46 ( xref ), and studies that reveal how UAF1 binds and activates USP12 and USP46 suggest that UAF1 will bind to USP1 in an analogous manner ( xref , xref )."
30456385
sparser
"The UAF1-binding SIM domain of FANCI is next to serines 559 and 565, so an alternative explanation is that ATR acts on these sites post-monoubiquitination, to prevent USP1:UAF1 binding."
32117957
reach
"Furthermore, the USP1–UAF1 complex has been shown to play critical roles in homologous recombination (10)."
30456385
reach
"We determined the ML323 induced change in deuterium incorporation (DeltaHDX) of the USP1 and UAF1 complex in the presence and absence of ML323."
24531842
sparser
"For the wild-type six-His-tagged USP1 coexpressed with untagged UAF1, the eluted fractions contained both USP1 and UAF1, suggesting that the wild-type USP1 can form a stable complex with UAF1 when expressed in insect cells."
23116119
reach
"Deubiquitination of FANCD2 may be attributed to the key role of USP1 and UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known."
27463890
sparser
"However, the I Ub D2 Ub substrate remained almost completely resistant to USP1‐UAF1 activity (Fig  xref A; Left )."
32510829
sparser
"Likewise, phosphorylation may affect how other FA proteins interact with ubiquitinated D2-I. For example, USP1-UAF1 interact less efficiently with phosphorylated D2-I xref ."
36050501
sparser
"Several findings have emerged, namely: (1) occurrence of USP1-UAF1 mediated-deubiquitination of FANCD2 on DNA; (2) identification of UAF1 amino acid residues important for DNA binding activity; (3) demonstration that UAF1 DNA binding as being required for FANCD2 deubiquitination within the context of the USP1-UAF1 complex; (4) documentation that DNA binding by RAD51AP1 can substitute for that of UAF1 in FANCD2 deubiquitination within the context of the trimeric USP1-UAF1-RAD51AP1 complex; and (5) revelation that UAF1 and RAD51AP1 provide redundant functions for FANCD2 deubiquitination in cells, thus uncovering a role of RAD51AP1 in the FA DNA damage response in addition to its well-documented DNA repair function."
31253762
biogrid
No evidence text available
23116119
biogrid
No evidence text available
19615732
reach
"If USP1 (235-408) S313D interacts weakly with UAF1, a negative result in the nuclear relocation assay may be due to competition by endogenous partner (s)."
25744535
reach
"An HTS using USP1 and UAF1 complex identified different inhibitors for this deubiquitinating enzyme complex [XREF_BIBR], and pimozide resulted to be the more efficient chemical against it."
26517048
reach
"The catalytic activity of the singly six-His-tagged USP1 and UAF1 complex that contained wild-type or mutant USP1 was assessed."
23116119
sparser
"FANCD2 monoubiquitination is temporally and spatially controlled at stalled forks by the FA core complex (a RING E3 ligase), USP1:UAF1 (a deubiquitinating enzyme) and ATR kinase ( xref )."
32117957
sparser
"In this way, USP1:UAF1 drives FANCI:FANCD2 complex toward a uniformly di-ubiquitinated state, that can only be de-ubiquitinated post-repair."
32117957
sparser
"Nevertheless, our work here shows that this ability of USP1‐UAF1 is compromised when FANCI is also ubiquitinated."
32510829
sparser
"Human USP1 forms a stable complex with UAF1 ( xref )."
22118673
sparser
"The purified UAF1-USP1 complex was indeed active in the Ub-AFC assay, and the activity was strongly and reversibly inhibited by H 2 O 2 ."
34177595
sparser
"Likewise, mutation of USP1 E444K, analogous to the impactful USP46 E186K mutation, abrogated WDR48 binding and stimulation of USP1 deubiquitinase activity."
26388029
sparser
"In the past years, several agents aimed at USP1 have been reported, such as pimozide and ML‐323. xref , xref These agents inhibit the activity of USP1‐WDR48 complex in a non‐competitive manner. xref In the present study, we demonstrated that siRNA‐USP1 transfection or ML‐323 treatment decreased the proliferation of HCC cells."
32951278
biogrid
No evidence text available
24850727
biogrid
No evidence text available
18082604
reach
"Once the USP1-UAF1 complex is formed, it translocates into the nucleus where the recruitment of FANCD2 and PCNA substrates using a SUMO-like domain takes a place to regulate DNA damage response [72]."
32512887
reach
"26 Hence, the significance of Elg1 's affinity for SUMO is not fully understood.Intriguingly, human ATAD5 appears to respond differently from its yeast counterpart to PCNA modifications : whereas no p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23688817
reach
"Our results are consistent with a model in which USP1 and UAF1 form a complex in the cytoplasm that is subsequently translocated to the nucleus through active nuclear import mediated by the two USP1 NLSs (XREF_FIG)."
22701671
reach
"Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1 and UAF1 Complex."
22701671
reach
"The USP1 and UAF1 complex purified from insect cells was reduced with 100 mM dithiothreitol, alkylated with 150 mM iodoacetamide, and then digested with trypsin at 37 degreesC overnight."
23116119
sparser
"To ask whether DNA is needed for deubiquitination, we treated the reaction mixture with benzonase to digest the DNA before adding USP1-UAF1 (Fig.  xref , lanes 5, 7, 9, and 11; Supplementary Fig.  xref , lanes 4–7)."
31253762
reach
"Once the lesion has been repaired, the ID complex is deubiquitinated by the USP1 and UAF1 complex, which also acts on monoubiquitinated PCNA when associated to the RFC subunit ELG1."
20965415
sparser
"In both USP1 and USP1‐UAF1, the enzyme is faster on DNA‐loaded PCNA‐Ub, but the increase in activity due to DNA loading is higher in the presence of UAF1: fivefold increase in USP1‐UAF1 and a twofold increase in USP1 alone (Table  xref , Fig  xref )."
33619839
reach
"The Usp1 and UAF1 complex is recruited to PCNA-Ub via an interaction of UAF1 with Elg1, an alternative component of the clamp loader."
22989887
reach
"In cluster 1, one of the highly ranked complexes searched against CORUM is the USP1 and UAF1 complex which was reported as a schizophrenic candidate complex, and its inhibitor, Pimozide, is one of the antipsychotics with the neuroleptic property of treating schizophrenic patients [XREF_BIBR]."
25522158
sparser
"Lastly, we present evidence that E1 promotes unidirectional replication not only through its association with UAF1-USP1 but also by binding to the Bloom (BLM) helicase."
30890612
reach
"[236] In contrast, USP1 forms a complex with UAF1 and enhances TLR3/4 and RIG-I-induced IRF3 activation and subsequent IFN-beta secretion by binding to TBK1 and removing its K48 linked polyubiquitin chains, thus preventing it from proteasomal degradation."
33511009
sparser
"We subsequently treated half of the substrate sample with benzonase nuclease to eliminate the DNA before subjecting both the nuclease-treated and untreated substrate samples to USP1–UAF1 activity."
30456385
sparser
"The effect of FANCI's ubiquitination may be on rendering the doubly ubiquitinated ID2 complex unamenable to USP1‐UAF1 modulation, for example by stabilizing an ID2 conformational change induced by FANCD2 ubiquitination or inducing further minor conformational changes that stabilize the complex."
32510829
reach
"For USP1 (S313A) and UAF1 complex, no band coressponding to the USP1 and UAF1 complex was detected."
23116119
reach
"The difference in cross linking pattern between the copurified USP1 and UAF1 complex and individually purified USP1 suggests that Ser313 likely undergoes dephosphorylation when being individually expressed and purified from insect cells."
23116119
reach
"In any case, HU counteracts USP1 and p21 with alternative strategies : USP1 interaction with its activating partner UAF1 is eliminated by HU and the interaction of p21 and PCNA is specifically prevented after HU."
23723248
sparser
"USP1-WDR48 deubiquitinase complex enhances TGF-β induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1."
33461373
reach
"Such a model, obviously, implies that USP1 can bind simultaneously to the nuclear import receptors and to UAF1."
22701671
reach
"The present identification of selective, noncompetitive inhibitors against the USP1 and UAF1 complex represents the first example of targeting the USP and WD40 repeat protein complex for inhibitor discovery."
22118673
reach
"However, the mechanisms that may modulate the nucleocytoplasmic localization of the USP1 and UAF1 complex have not yet been studied."
22701671
reach
"We observed a slightly lower k cat for USP1 (S313D) and UAF1 complex (0.084 s -1) compared to the wild-type USP1 and UAF1 complex (0.096 s -1)."
23116119
sparser
"Lastly, FANCD2 is deubiquitinated by USP1–UAF1 complex to terminate the FA pathway ( xref , xref )."
33693881
sparser
"Removal of the ubiquitin signal from FANCD2 is conducted by the USP1–UAF1 DUB, and disruption of USP1 catalytic activity results in an accumulation of FANCD2-Ub and FA-like phenotypes ( xref , xref , xref , xref )."
30456385
reach
"Upon formation of a USP1 and UAF1 complex, the catalytic activity of USP1 is greatly stimulated."
22118673
reach
"In addition, we confirmed the interaction between USP1 and WDR48 in HCC cell lines using co‐immunoprecipitation, and the results showed that USP1 interacted with WDR48 in MHCC97H and SK‐Hep‐1 cells (Figure 10H).3.9 SiRNA-USP1 transfection or ML-323 treatment decreased the proliferation of HCC cells."
32951278
reach
"However, other DUBs resulted to be inhibited by this same compound, thus, the effects seen by using it in cells could not be imputed to the specific inhibition of USP1 and UAF1 complex."
26517048
sparser
"Hence, we hypothesized that the USP1‐WDR48 complex played critical roles in HCC by stabilizing the activity of their substrates."
32951278
sparser
"To assemble I Ub D2 Ub ‐DNA complex with ubiquitin mutants on FANCI, we added D2 Ub to each ubiquitin‐mutated I Ub and subjected the resulting I Ub D2 Ub ‐DNA complex to deubiquitination treatment with USP1‐UAF1 (Fig  xref E)."
32510829
reach
"On the other hand, our findings provide the basis for a relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1 and UAF1 complex and thus interfere with the activity of this complex in tumor cells."
22701671
reach
"10 The USP1 and UAF1 complex has been shown to regulate the tolerance of DNA damage induced by DNA cross linking agents through deubiquitination of PCNA (proliferating cell nuclear antigen) 11 and FANCD2 (Fanconi anemia complementation group D2), 12 which are proteins that function in translesion synthesis and the Fanconi anemia pathway, respectively."
25229643
reach
"There is evidence that suggests that the USP1 and UAF1 complex, previously discussed above to be involved in the FA pathway and TLS, promotes DSB repair via HR."
30831436
reach
"A 227-fold decrease in k cat / K m was evident when compared to the wild-type USP1 and UAF1 complex."
23116119
reach
"incubation on ice, 400 nM of the USP1 and UAF1 complex (Boston Biochem, E-568) was added."
32269332
reach
"The amount of FANCA in chromatin is affected in the former cell line but not in the latter.The de and ubiquitinase complex USP1 and UAF1 [86,87] counteracts the mono-ubiquitination of FANCD2-FANCI."
28552166
reach
"The deubiquitinating enzyme heterodimeric complex USP1 and UAF1 regulates the Fanconi anemia (FA) DNA repair pathway."
24001775
reach
"Finally, in the last step, the deubiquitinating (DUB) complex USP1 and UAF1 removes monoubiquitin from the ID complex, allowing for pathway regeneration."
27148358
sparser
"The USP1-UAF1 inhibitor ML323 suppresses the expression of IFN-β and enhances virus replication in vitro and in vivo ."
35283827
reach
"A study in which USP1 -/-, UAF1 -/-/-, and USP1 -/- UAF1 -/-/- double-knockout DT40 cells showed hypersensitivity to camptothecin and an inhibitor of poly (ADP-ribose) polymerase (PARP), which suggests that the USP1 and UAF1 complex promotes HR."
30831436
reach
"Deubiquitination of FANCD2 and FANCI by the constitutively active deubiquitinating complex UAF1 and USP1 keeps the pathway turned off unless required [XREF_BIBR]."
29017571
sparser
"Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex."
27463890
sparser
"To determine whether this domain contributes to the interaction between USP1 and UAF1, a truncated USP1 (amino acids 235-408) (USP1_ID) with a N-terminal GST fusion was generated for pull-down assay with UAF1."
23116119
sparser
"However if FANCD2- Ub -FANCI- Ub is dissociated from DNA, it then becomes a USP1:UAF1 substrate ( xref )."
32117957
reach
"USP1 Ser313 phosphorylation promotes complex formation between USP1 and UAF1."
23116119
sparser
"The USP1-UAF1 protein complex is an important regulator in DNA damage response pathways [ xref ]."
33498168
reach
"Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs."
22701671
reach
"The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI."
36653190
sparser
"USP1‐UAF1, at low (25 nM) concentrations, deubiquitinated both D2 Ub and ID2 Ub at similar rates."
32510829
reach
"We ruled out the possibility that ML323 acts as a disruptor of the USP1 and UAF1 complex by native gel analysis of USP1-UAF1 incubated with varied concentrations of ML323 up to 100 times its IC 50 (XREF_SUPPLEMENTARY)."
24531842
reach
"This hyper-activation is not observed for the USP1 and UAF1 complex."
27650958
sparser
"In particular, FANCI itself is a target for monoubiquitination by the FA core complex ( xref ), is a substrate of ATR kinase ( xref ) and contains a USP1:UAF1 binding site necessary for deubiquitination of FANCD2 ( xref )."
32117957
sparser
"However, USP1–UAF1 targets multiple substrates, including the inhibitor of DNA-binding proteins and TBK1, meaning a catalytic activity inhibitor may affect multiple processes."
30456385
sparser
"These results, collectively with our observation that SIVA1 depletion did not affect the chromatin association of USP1 and UAF1 ( xref ), exclude the possibility that SIVA1 may act as an antagonist of PCNA deubiquitination by the USP1–UAF1 complex."
24958773
sparser
"To test this, we purified xl FANCD2-Ub to homogeneity ( xref ) and assayed with human USP1–UAF1."
30456385
biogrid
No evidence text available
27239033
reach
"UAF1 is a WD40-repeat containing protein that also binds to and regulates two other DUBs, USP12 and USP46 [XREF_BIBR], but its best characterized role is as a USP1 cofactor in the context of a USP1 and UAF1 complex."
23937906
reach
"Collectively, these data illustrate the dynamic changes of UAF1 and USP1 expression during viral infection, suggesting that USP1 and UAF1 complex is potentially involved in the regulation of antiviral responses."
29138248
reach
"This has already been evidenced by the development of therapeutics aimed at the Usp1 and Uaf-1 complex, which have been shown to reverse cisplatin-resistance in non small lung cancer cells [XREF_BIBR, XREF_BIBR]."
26462181
sparser
"In addition, we confirmed the interaction between USP1 and WDR48 in HCC cell lines using co‐immunoprecipitation, and the results showed that USP1 interacted with WDR48 in MHCC97H and SK‐Hep‐1 cells (Figure  xref )."
32951278
reach
"As is well known, active transcription foci are distributed in the nucleus in a punctate pattern; therefore, USP1, WDR48, KDM4A, and AR might form a complex to regulate transcription in PC cells."
32133742
reach
"A recent publication features the crystal structure of human USP1-UAF1 complex with and without ubiquitin, and one that is bound to monoubiquitinated FANCI-FANCD2 59 ."
35365626
sparser
"This finding suggested that the USP1‐WDR48 complex played a tumour‐promoting role in HCC by stabilizing and deubiquitinating these hub genes."
32951278
reach
"Furthermore, the USP1 and UAF1 complex can readily, and rapidly, de-ubiquitinate mono-ubiquitinated FANCD2 in an in vitro de-ubiquitination reaction [XREF_BIBR]."
19101576
reach
"In addition to providing further insight into the biological consequences of the USP1 and UAF1 interaction, the results presented here have practical implications for the development of the USP1 and UAF1 as an anticancer target."
22701671
sparser
"However, the action of USP1‐UAF1 within the cell will allow a population of ID2 Ub to revert to an open state via the unstable closed state of deubiquitinated ID2."
32510829
sparser
"Although we showed that FANCD2-Ub with FANCI and DNA does not obviously affect USP1–UAF1 deubiquitination in vitro, FANCI has been shown to regulate FANCD2 deubiquitination in cells via phosphomimetic mutations ( xref ) and SUMO-like interacting motif mutations ( xref )."
30456385
reach
"Notably, ML323 did not inhibit the USP46 and UAF1 complex that contains the same UAF1 subunit as the USP1 and UAF1 complex and demonstrated little inhibition against USP1 alone (IC 50> 200 muM) in a Ub-Rho assay in which USP1-UAF1 and USP1 demonstrated similar K m values."
24531842
sparser
"Moreover, H 2 O 2 treatment did not affect the association of Usp1 with UAF1 ( xref ), suggesting that inhibition of USP1 by oxidative stress is not likely caused by ROS-mediated disruption of the Usp1-UAF1 complex."
23219552
sparser
"Removal of the ubiquitins, on FANCI and FANCD2, is also critical for the FA pathway, and this deubiquitination step is catalysed by the USP1‐UAF1 complex xref , xref ."
32510829
sparser
"However, the resulting di-mono-ubiquitinated complex is highly resistant to USP1-UAF1 deubiquitination."
34137174
reach
"The binding of Uaf1 to Usp1 DUB strongly increases its deubiquitylating activity."
23159736
sparser
"To date, how USP1 and UAF1 interact and how the formation of the USP1/UAF1 complex is regulated remains largely unknown."
23116119
sparser
"As reported, USP1 alone had low deubiquitinase activity, and its activity was significantly promoted when forming a complex with its binding partner WDR48 . xref USP1‐WDR48 mainly works by maintaining the activity of their substrates."
32951278
reach
"The USP1 and UAF1 complex reduces the accumulation of mono-ubiquitinated PCNA during normal cell division, which prevents mutagenesis by error-prone TLS polymerases."
25795125
sparser
"UAF1-USP1 sustains an innate immune response through the phosphorylation and activation of signal transducer and activator of transcription-1 (pSTAT1), as well as regulates the DNA damage response."
36798153
sparser
"DNA binding was shown to promote USP1‐UAF1 activity on FANCD2‐Ub, but in this case, activation is dependent on a DNA‐binding role of UAF1 (Liang et al , xref )."
33619839
reach
"Recently, PCNA deubiquitylation by the USP1 and UAF1 complex in conjunction with ELG1, which directs the USP1-UAF1 to ubiquitin-PCNA, has emerged as an important regulatory mechanism of damage bypass."
22987070