IndraLab

Statements


7 1 | 23 31

sparser
"Meitinger et al. performed a genome-wide CRISPR/Cas9 screen in RPE-1 cells and identified a 53BP1-USP28 module which induces G1-phase cell cycle arrest after centrosome loss ( xref )."

sparser
"Using this antibody we examined the association of endogenous USP28 and 53BP1 ( Figure 1 C)."

sparser
"As shown in Figures 1 D and 1E, 53BP1 specifically interacts with USP28 but not USP25 or USP7."

sparser
"DNA damage did not dramatically change the interaction between USP28 and 53BP1 ( Figure 1 F)."

reach
"USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers."

reach
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats."

reach
"Furthermore, a 53BP1-USP28 complex was identified as an activator of p53-mediated transactivation (Cuella-Martin et al., 2016a, Fong et al., 2016, Lambrus et al., 2016, Meitinger et al., 2016)."

sparser
"Indeed, work from the Holland, Oegema, and Tsou laboratories has implicated the 53BP1-USP28 module in the p53-dependent response to prolonged mitotic arrest and to numerical centrosomal abnormalities [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We verified the binding and specificity of the interactions between USP28 and 53BP1 by transiently expressing HA-USP28, HA-USP25, or HA-USP7 in 293T cells."

sparser
"Activation of p53-transcription by TIRR depletion relied on 53BP1-TTD interactions with p53-K382me2 and USP28, however it remains unclear if USP28 interacts with 53BP1 in this context ( xref )."

reach
"Our mass spectrometry analysis and followup immunoprecipitation assays showed that USP28 interacts with 53BP1 in unstressed cells (Supplementary Figure S5A and B), suggesting a role for the 53BP1USP28 complex during unperturbed cell cycle (41,65)."

reach
"The molecular underpinnings of the disassembly of 53BP1USP28 complexes upon genotoxic stress remain to be investigated but can involve proteasomal degradation of 53BP1 (93) or its recruitment to modified histones at DNA damage sites (3), which could sterically interfere with USP28 binding.In our model, dimerization of USP28 limits unscheduled DNA replication at transcriptionally active loci by preventing ectopic recruitment of PAF1 to MYC."

reach
"USP28 binds to 53BP1, an essential protein required for the stabilization of the Chk2-p53-PUMA repair pathway [150] ."

reach
"Remarkably, the interaction between 53BP1 and USP28 was completely abolished by the G1560K mutation and largely diminished by the V1544I mutation, while the G1593K mutation increased 53BP1 binding to USP28, thus acting as a GOF mutation (Figure 3F)."

sparser
"Remarkably, the interaction between 53BP1 and USP28 was completely abolished by the G1560K mutation and largely diminished by the V1544I mutation, while the G1593K mutation increased 53BP1 binding to USP28, thus acting as a GOF mutation ( xref )."

reach
"The largest class is composed of high-confidence interacting proteins that only bind a single DUB (for example, p53 binding protein 1 or 53BP1, which binds to USP28)."

sparser
"USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers."

reach
"Taken together, a body of evidence supports a model in which a 53BP1 and USP28 complex modulates p53 activity in response to centrosome loss."

sparser
"It was previously reported that USP28 is involved in the regulation of TP53 protein abundance in a USP28TP53BP1 cell cycle‐dependent fashion (Fong et al , xref ; Lambrus et al , xref ; Meitinger et al , xref )."

reach
"Important future directions include dissecting the interactions between 53BP1 and USP28 that activate downstream p53-p21 signaling, as well as screening for the upstream components that transduce the signal (see Outstanding Questions)."

sparser
"Genotoxic stress diminishes 53BP1USP28 interaction, promotes disassembly of USP28 dimers and stimulates PAF1c recruitment by MYC."

sparser
"Furthermore, a 53BP1-USP28 complex was identified as an activator of p53-mediated transactivation ( xref , xref , xref , xref )."

sparser
"Our mass spectrometry analysis and followup immunoprecipitation assays showed that USP28 interacts with 53BP1 in unstressed cells ( xref ), suggesting a role for the 53BP1USP28 complex during unperturbed cell cycle ( xref , xref )."

sparser
"Here, we describe the TTD as the second 53BP1 domain, in addition to the tandem BRCT, that regulates the USP2853BP1 interaction ( xref ) ( xref ; xref )."

sparser
"In particular, the TTD residues V1544 and G1560, located opposite to the methyl-K/R binding pocket ( xref ) ( xref ), define a non-canonical TTD interaction surface that promotes the association of 53BP1 with USP28."

sparser
"Strikingly, PLA and immunoprecipitation assays showed that 53BP1 selectively binds wildtype but not monomeric USP28 (Figure xref and  xref ; xref )."

sparser
"Etoposide treatment diminished 53BP1-USP28 interaction in an ATM-dependent manner (Figure xref ; xref ), correlating with the disruption of USP28 dimers."

sparser
"It is also unclear how the 53BP1-USP28 axis regulates p53-dependent tumor suppression, as mice lacking Usp28 are not overtly cancer prone ( Knobel et al., 2014 )."

reach
"We show here that mitotic extension leads to the formation of p53-binding protein 1 (53BP1)-ubiquitin-specific protease 28 (USP28)-p53 protein complexes that are transmitted to, and stably retained by, daughter cells."

reach
"USP28 phosphorylation regulates the complex formation of DNA checkpoint proteins and binds to checkpoint proteins 53BP1, Claspin, and MDC1, resulting in repairing DNA damage."

sparser
"We found that 53BP1 binding to USP28 was specifically attenuated by the R1811A BRCT mutation, yet unaffected by the K1814M phospho-binding or p53-binding mutations ( xref D)."

sparser
"Different from the interaction of USP28 with LSD1, USP28-mediated p53BP1 stabilization only occurs after DNA damage and no effect is found in the absence of DNA damage, suggesting that the interaction between USP28 with p53BP1 is regulated by DNA damaging."

sparser
"53BP1 selectively interacts with USP28 dimers and depletion of 53BP1 favors USP28 monomers, suggesting that 53BP1 stabilizes the dimeric conformation of USP28."

sparser
"The 53BP1USP28 interaction is diminished upon genotoxic stress in an ATM-dependent manner, leading to formation of USP28 monomers and stabilization of MYC."

sparser
"The molecular underpinnings of the disassembly of 53BP1USP28 complexes upon genotoxic stress remain to be investigated but can involve proteasomal degradation of 53BP1 ( xref ) or its recruitment to modified histones at DNA damage sites ( xref ), which could sterically interfere with USP28 binding."

reach
"The MSP, as well as the transcriptional response to N3 or DSBs (IR or TOP2 inhibition) requires interactions between the 53BP1-TTD and USP28, as well as the 53BP1-BRCT and p53 (Figure 1A)."

reach
"This would be consistent with a putative cooperation between p53, 53BP1, and USP28 in tumor suppression."

reach
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28 dependent deubiquitination and activation of p53, leading to cell cycle arrest XREF_BIBR, XREF_BIBR (XREF_FIG)."

sparser
"In this case, the MDM2 p60 fragment that is known to interact with and stabilize p53 ( xref ) might be redundant with the function of 53BP1-USP28."

reach
"We verified the binding and specificity of the interactions between USP28 and 53BP1 by transiently expressing HA-USP28, HA-USP25, or HA-USP7 in 293T cells."

sparser
"While these results may suggest that 53BP1-USP28 could act as p53 transcriptional cofactors, Cuella-Martin et al. (2016) failed to detect 53BP1 binding to p53-responsive promoters, instead suggesting [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"DNA damage did not dramatically change the interaction between USP28 and 53BP1 ( Figure 1 F)."

sparser
"USP28 binds 53BP1 and has been implicated previously in the DDR and apoptosis following IR."

sparser
"Interaction with ATM contributes to the binding of USP28 to TP53BP1, the overall role of USP28 in DNA damage signaling, however, was unclear [ xref ]."

sparser
"USP28 has been reported to regulate TP53 abundance in a USP28-TP53BP1 cell cycle-dependent fashion [ xref – xref ]."

reach
"Even after DNA damage, where USP28 recruitment to 53BP1 foci is visible, a stable MSP complex was not detected and mutations in the BRCT or TTD domains of 53BP1 selectively disrupted the p53 and USP28 interactions, respectively (Meitinger et al., 2024; Knobel et al., 2014)."

sparser
"Thus, consistent with the known interaction of 53BP1 with USP28, we show that while 53BP1 has no deubiquitinase activity, it can function upstream of USP28 to stabilize p53."

reach
"We found that 53BP1 binding to USP28 was specifically attenuated by the R1811A BRCT mutation, yet unaffected by the K1814M phospho binding or p53 binding mutations (XREF_FIG D)."

reach
"The cooperation between 53BP1 and USP28 in triggering p53 dependent growth arrest following N3 treatments prompted us to investigate their function in arresting the cell cycle in response to DNA damage."

reach
"Moreover, USP28 binds checkpoint proteins 53BP1, Claspin, and Mdc1 [XREF_BIBR]."

reach
"For example, the DNA damage response pathway is central to the maintenance of genomic stability and both members of a key DDR complex, the TP53BP1 and USP28 complex, which are substrates of the ATM kinase, were identified within the top 110 TSGs (q-value < 0.15, XREF_FIG, XREF_FIG)."

sparser
"Finally, disruption of centrosomal function, which may be produced by many MCPH mutations ( xref ), may stimulate P53 activity through the 53BP1-USP28 axis ( xref ; xref )."

sparser
"The PLK1-regulated p53BP1 and USP28 stopwatch complex appears to accumulate more slowly becoming detectable from 2–4 h arrest in mitosis xref , suggesting this may reinforce the loss of MDM2 during longer mitotic delays."

reach
"USP28 binds 53BP1 and has been implicated previously in the DDR and apoptosis following IR."