IndraLab

Statements

USP28 binds FBXW7. 51 / 51
1 | 18 32
sparser
"Loss of the USP28-FBW7."
40872623
sparser
"Loss of the USP28-FBW7 complex."
32273491
reach
"Discovery of an analog of the Fbw7 and Usp28 complex in Drosophila demonstrates that such complexes represent an evolutionary conserved regulatory paradigm (Li et al., 2013)."
25437563
reach
"Past investigations revealed that although many FBW7 domains, including WD40, promoted FBW7’s binding to USP28, the amino terminus of FBW7 contributed to the interaction of FBW7, c-Myc and USP28 [5, 29]."
36879346
sparser
"Therefore, the loss of the USP28-FBW7 complex could stabilize BRAF to potentiate activating downstream MAPK pathway, promoting the therapeutic resistance to BRAF-targeted therapy."
32273491
sparser
"Several mechanisms of intrinsic resistance have been described among whom loss of PTEN, cyclin D1 amplification, loss of NF1, RAC1 P29S mutation, HGF secretion, MAP3K8 overexpression, loss of the USP28–FBW7 complex, low levels of CD8 tumor-infiltrating T cells and increased expression of the immune inhibitory molecule PD-L1 ( xref – xref )."
34136385
sparser
"Collectively, the loss of USP28-FBW7 complex-mediated BRAF degradation stimulates the intrinsic resistance to MAPK inhibition targeted therapy in melanoma [ xref , xref ]."
32273491
reach
"In case of the Fbw7 and Usp28 complex, we suggest that wiring control of the ligase and its substrates to a single DUB ensures that stabilization of proto-oncoproteins during homeostatic processes occ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25437563
sparser
"Due to mutations in RAC1, loss of PTEN, NF1, CCND1, USP28-FBW7 complex, COT overexpression, and CCND1 amplification, the BRAF kinase enzyme developed resistance over the commercially available BRAF inhibitors."
37470921
sparser
"USP28 can bind to FBXW7 and inhibit ubiquitination modification of c-Myc by the latter, thus increasing the protein stability of c-Myc ( xref )."
32724394
sparser
"Past investigations revealed that although many FBW7 domains, including WD40, promoted FBW7’s binding to USP28, the amino terminus of FBW7 contributed to the interaction of FBW7, c-Myc and USP28 [ xref , xref ]."
36879346
sparser
"Genetic alterations, including loss of PTEN , amplification of CCND1 , loss of NF1 , RAC mutations, and loss of the USP28-FBW7 complex, have been identified in the development of intrinsic resistance."
32273491
reach
"Usp28 preferentially binds the Fbw7α isoform, whereas Usp36 selectively associates with Fbw7γ and both DUBs stabilize Myc."
26459133
reach
"We decided to focus our attention on USP28, as USP28 forms a complex with FBW7, a protein recently described to be mutated in melanoma."
29880484
biogrid
No evidence text available
17558397
reach
"USP28 also interacted with FBW7 under physiological conditions, as seen by endogenous FBW7 coimmunoprecipitating with endogenous USP28."
29880484
sparser
"One interesting corollary of these findings was that an alternative to the ‘piggyback’ model of USP28 binding to substrates via Fbw7 must be acting in Fbw7-deleted animals."
26410034
reach
"Next, to study the effect of FBW7 and USP28 complex on BRAF ubiquitination, we cotransfected BRAF with either wild-type FBW7 or FBW7 (R505L)-binding mutant and analyzed endogenous BRAF ubiquitination levels."
29880484
reach
"Interestingly, the frequency of coalterations between USP28 and FBW7 is low (0.05%; 2/39) indicating that nearly 13% (37/287) of all melanoma patients contain mutations within the FBW7 and USP28 complex."
29880484
sparser
"Pulldown experiments using c-Myc peptides showed that USP28 and Fbw7 bind to the phosphorylated CPD motif; however, USP28 only bound to non-phosphorylated peptide in the absence of Fbw7 [91] ."
26410034
reach
"USP28 also binds the E3 ubiquitin ligase FBW7 to stabilize MYC and promote cell proliferation [33] ( Fig. 3 a)."
37245535
sparser
"In unstressed cells, Usp28 forms a complex with Fbw7 and antagonizes substrate ubiquitination, whereas after DNA damage this complex dissociates, promoting Fbw7-dependent substrate degradation ( Popov[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25437563
sparser
"However, the functional significance of the USP28-FBXW7 partnership in maintaining SOX9 stability remains unexplored."
40240356
reach
"31 In another similar study, cross‐linked ORF in circFBXW7, driven by the IRES, was found to encode a new 21‐kDa protein called FBXW7‐185aa.61 FBXW7‐185aa can bind with USP28 to prevent USP28 binding with FBXW7α mRNA, thereby reducing the half‐life of c‐Myc and inhibiting proliferation and cell cycle progression, significantly inhibiting glioma progression (Figure 3C).61 5."
31599076
reach
"USP28 binds to substrates such as c-MYC, c-JUN, and NOTCH1 through interaction with FBXW7, and it stabilizes these proteins by reversing their ubiquitylation catalyzed by SCF FBXW7 ."
32113998
sparser
"However, interaction of FBXW7 with USP28 was not impaired by deletion of the WD40 domain and was also shown in the absence of NOTCH1 in HEK293 NOTCH1 knockout cells (Fig.  xref )."
40456839
sparser
"Additionally, USP28 forms complex with FBXW7 for binding to its catalytic substrate Ubiquitin ( Popov, Wanzel et al. 2007 )."
32028107
sparser
"Thus, FBW7-USP28 seems to work together to maintain the homeostasis of these proteins ( xref )."
37230388
sparser
"In unstressed cells, USP28 forms a complex with FBXW7 and antagonizes substrate ubiquitination, however, after DNA damage this complex dissociates promoting FBXW7-dependent substrate degradation []."
30209015
sparser
"USP28 also binds the E3 ubiquitin ligase FBW7 to stabilize MYC and promote cell proliferation [33] ( Fig. 3 a)."
37245535
reach
"ChemMine Tools was used for performing structural clustering of the best scoring ligands from both sets of results obtained in our study i.e. Ub binding region of USP28 and FBXW7 binding region of USP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32028107
reach
"Though ZDOCK and ClusPro gave different binding conformation of FBXW7 to the same UCID region of USP28, Pepsite2 validated that WD repeat region of FBXW7 binds to USP28 which was predicted by ZDOCK ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32028107
sparser
"Though ZDOCK and ClusPro gave different binding conformation of FBXW7 to the same UCID region of USP28, Pepsite2 validated that WD repeat region of FBXW7 binds to USP28 which was predicted by ZDOCK ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32028107
sparser
"Here we show that USP28 interacts with FBXW7 independently of the FBXW7 WD40 domain which confirms previous findings [ xref ]."
40456839
reach
"Due to mutations in RAC1, loss of PTEN, NF1, CCND1, USP28-FBW7 complex, COT overexpression, and CCND1 amplification, the BRAF kinase enzyme developed resistance over the commercially available BRAF inhibitors."
37470921
sparser
"Among the mechanisms underlying this phenomenon, several genetic alterations have been identified, including loss of PTEN or NF1 genes, CCND1 gene amplification, COT (MAP3K8) overexpression RAC1 mutation, and the disruption of the USP28-FBW7 complex."
40872623
reach
"The protein FBXW7-185aa functions as a tumor suppressor by competitively binding with USP28, and preventing USP28 binding to FBXW7α, subsequently inhibiting USP28-induced c-myc stabilization."
30111313
reach
"For example, USP28 and USP36 interact with FBW7 and reverse FBW7-mediated c-Myc degradation ( Popov et al., 2007 ; Sun et al., 2015 )."
34102342
sparser
"Usp28 binds to Fbw7, and Usp28 was shown to be recruited to c-Myc protein indirectly through Fbw7 (the “piggyback” model) ( xref )."
25716680
sparser
"In the context of melanoma, the loss of USP28-FBW7 complex has been identified as a significant mechanism to BRAFi in the treatment of metastatic melanoma: it causes the accumulation of oncogenic proteins, such as MYC, whose stability is normally regulated by FBW7."
40872623
sparser
"Previous work has shown that Usp28 interacts with its substrates via binding to Fbw7 ( xref )."
25716680
sparser
"We decided to focus our attention on USP28, as USP28 forms a complex with FBW7, a protein recently described to be mutated in melanoma ( xref ; xref )."
29880484
sparser
"Despite its initial success, resistance to BRAF inhibitors such as dabrafenib has emerged because of various factors, such as loss of PTEN, NF1, or USP28-FBW7, CCND1 amplification, COT overexpression, and mutations in RAC1 [ xref ]."
40141188
sparser
"USP28 also interacted with FBW7 under physiological conditions, as seen by endogenous FBW7 coimmunoprecipitating with endogenous USP28 (Fig. S2 H)."
29880484
sparser
"This type of resistance involves several key mechanisms ( xref ), including the loss of the phosphatase and TENsin homolog ( PTEN ) gene, amplification of the cyclin D1 ( CCND1 ) gene, Cancer Osaka Thyroid kinase (COT, MAP3K8) overexpression, loss of the neurofibromin 1 ( NF1 ) tumor suppressor gene, mutations in Ras-related C3 botulinum toxin substrate 1 (RAC1P29S), and the disruption of the ubiquitin-specific peptidase 28 (USP28-FBW7) complex."
40872623
sparser
"These data suggest that the unphosphorylated degron motif can mediate Usp28 binding in the absence of Fbw7 ( xref )."
25716680
reach
"Meanwhile, the activity of FBXW7 can be antagonized by USP28, which binds directly to FBXW7 [24, 25]."
40240356
sparser
"Loss of USP28-FBW7 also contributes to resistance by inhibiting the degradation of other proteins involved in cell survival, such as NOTCH1 ( xref )."
40872623
sparser
"Alternatively, USP21 could be acting directly to deubiquitylate the substrates of the cullin RING ligase, in an analogous fashion to USP28, which associates with the cullin-1-adapter FBW7 to deubiquitylate a range of substrates, including MYC ( xref )."
27621083
sparser
"Studies have identified the molecular mechanisms responsible for the intrinsic resistance include loss of PTEN , loss of NF1, CCND1 amplification, COT overexpression, mutations in RAC1 , and loss of the USP28-FBW7 complex [ xref , xref – xref ]."
32273491
reach
"USP28 interacts with and deubiquitinates FBW7 leading to the stability of FBW7 and consequently promoting degradation of FBW7 substrates."
30263945