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USP28 binds TP53BP1. 76 / 76
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"We further investigated the minimal region required for the interaction between USP28 and 53BP1."
41365927
sparser
"Using this antibody we examined the association of endogenous USP28 and 53BP1 ( Figure 1 C)."
16901786
hprd
No evidence text available
16901786
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 )."
32269206
sparser
"As shown in Figures 1 D and 1E, 53BP1 specifically interacts with USP28 but not USP25 or USP7."
16901786
sparser
"DNA damage did not dramatically change the interaction between USP28 and 53BP1 ( Figure 1 F)."
16901786
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"USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers."
38227944
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 )."
39398482
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 53BP1–USP28 complex during unperturbed cell cycle (41,65)."
38227944
reach
"The molecular underpinnings of the disassembly of 53BP1–USP28 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."
38227944
sparser
"Moreover, our results show that the interaction between 53BP1 and the chemically enforced dimer of the USP28 C-terminus remains stable after mitosis, mirroring the behavior of full-length USP28 (Fig.  xref )."
41365927
sparser
"These results suggest two possible mechanisms: either dimerization of USP28 is required for the interaction between the C-terminus of USP28 and 53BP1, or the dimerization arms create a second binding surface for 53BP1."
41365927
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"USP28 binds to 53BP1, an essential protein required for the stabilization of the Chk2-p53-PUMA repair pathway [150] ."
25481051
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"It was previously reported that USP28 is involved in the regulation of TP53 protein abundance in a USP28‐TP53BP1 cell cycle‐dependent fashion (Fong et al , xref ; Lambrus et al , xref ; Meitinger et al , xref )."
32128997
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"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)."
28188027
sparser
"USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers."
38227944
sparser
"Genotoxic stress diminishes 53BP1–USP28 interaction, promotes disassembly of USP28 dimers and stimulates PAF1c recruitment by MYC."
38227944
sparser
"We further observed that cancer cells frequently disrupt the USP28–53BP1 interaction, potentially as a strategy to bypass p53-mediated cell cycle arrest or apoptosis (Fig.  xref )."
41365927
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 )."
33606978
sparser
"In contrast, our findings reveal a distinct pathway in which mitotic stress enhances the interaction between USP28 and 53BP1, leading to the stabilization of p53 and the downregulation of MYC."
41365927
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"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)."
19632171
sparser
"This suggests that either 53BP1 is the relevant PLK1 target, or that alternative mechanisms regulate the interaction between 53BP1 and USP28 xref ."
41365927
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)."
33961797
reach
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats."
27432896
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]"
27716486
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."
16901786
sparser
"It is surprising that USP28 would co-IP with GMCL1 (presumably because USP28 is bound to 53BP1) if the function of GMCL1-53BP1 interaction is to promote 53BP1 degradation."
41553759
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)."
33606978
sparser
"USP28 and 53BP1 proteins form a complex to stabilise the tumour suppressor p53, which is required to protect cells from mitotic stress and subsequent genome instability."
41365927
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"Taken together, a body of evidence supports a model in which a 53BP1 and USP28 complex modulates p53 activity in response to centrosome loss."
28188027
sparser
"Strikingly, PLA and immunoprecipitation assays showed that 53BP1 selectively binds wildtype but not monomeric USP28 (Figure xref and  xref ; xref )."
38227944
sparser
"Etoposide treatment diminished 53BP1-USP28 interaction in an ATM-dependent manner (Figure xref ; xref ), correlating with the disruption of USP28 dimers."
38227944
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 )."
27716486
biogrid
No evidence text available
33606978
sparser
"Furthermore, a 53BP1-USP28 complex was identified as an activator of p53-mediated transactivation ( xref , xref , xref , xref )."
33961797
sparser
"Our mass spectrometry analysis and followup immunoprecipitation assays showed that USP28 interacts with 53BP1 in unstressed cells ( xref ), suggesting a role for the 53BP1–USP28 complex during unperturbed cell cycle ( xref , xref )."
38227944
sparser
"Here, we describe the TTD as the second 53BP1 domain, in addition to the tandem BRCT, that regulates the USP28–53BP1 interaction ( xref ) ( xref ; xref )."
33606978
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."
33606978
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."
38547292
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"USP28 phosphorylation regulates the complex formation of DNA checkpoint proteins and binds to checkpoint proteins 53BP1, Claspin, and MDC1, resulting in repairing DNA damage."
37245535
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"RPE1 cells harboring the 53BP1 G1560K mutation, which disrupts USP28 binding, phenocopied USP28 deletion, suggesting that these effects rely on the USP28–53BP1 interaction xref , xref ."
41365927
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)."
27546791
biogrid
No evidence text available
27546791
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."
24075993
sparser
"53BP1 selectively interacts with USP28 dimers and depletion of 53BP1 favors USP28 monomers, suggesting that 53BP1 stabilizes the dimeric conformation of USP28."
38227944
sparser
"The 53BP1–USP28 interaction is diminished upon genotoxic stress in an ATM-dependent manner, leading to formation of USP28 monomers and stabilization of MYC."
38227944
sparser
"The molecular underpinnings of the disassembly of 53BP1–USP28 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."
38227944
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)."
39398482
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)."
39398482
biogrid
No evidence text available
29656893
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."
27371829
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)."
27546791
sparser
"Evidence linking mitotic delays induced by activation of the spindle assembly checkpoint with positive and negative regulators of the G1 DNA damage checkpoint target p53 is discussed, with a focus on time-dependent changes to a p53-binding deubiquitinating complex USP28-53BP1 and the p53 ubiquitin-ligase mouse double minute homologue 2 (MDM2), respectively."
40628545
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."
27546791
reach
"This would be consistent with a putative cooperation between p53, 53BP1, and USP28 in tumor suppression."
27546791
sparser
"MDM2 and USP28-53BP1 therefore work together to set the threshold for p53-dependent cell cycle arrest in G1 cells following delays in mitosis."
40551011
sparser
"To determine whether the 53BP1-USP28 hIF2 complexes could activate p53 in response to prolonged mitosis, we treated cells with PLK4i to induce centrosome depletion and thereby prolong mitosis (Fig.  xref ) xref , xref ."
41365927
biogrid
No evidence text available
16901786
biogrid
No evidence text available
16901786
biogrid
No evidence text available
16901786
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)."
29363672
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."
35758262
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."
16901786
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]"
27716486
reach
"DNA damage did not dramatically change the interaction between USP28 and 53BP1 ( Figure 1 F)."
16901786
sparser
"The kinase PLK1 is essential for the interaction between USP28 and 53BP1 (Fig.  xref ) xref ."
41365927
sparser
"Disruption of dimerization through two mutations (V541E, L545E) impaired USP28’s interaction with 53BP1, suggesting that USP28 must form a dimer to interact with 53BP1 (Fig.  xref )."
41365927
sparser
"USP28 binds 53BP1 and has been implicated previously in the DDR and apoptosis following IR."
29089421
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 ]."
34611298
sparser
"USP28 has been reported to regulate TP53 abundance in a USP28-TP53BP1 cell cycle-dependent fashion [ xref – xref ]."
34611298
reach
"Moreover, USP28 binds checkpoint proteins 53BP1, Claspin, and Mdc1 [XREF_BIBR]."
21480003
biogrid
No evidence text available
19615732
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)."
24183448
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 )."
37457016
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."
39789219
reach
"USP28 binds 53BP1 and has been implicated previously in the DDR and apoptosis following IR."
29089421