IndraLab

Statements

USP28 affects TP53
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USP28 activates TP53.
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USP28 activates TP53. 10 / 39
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"Following p53 localization under such conditions, 53BP1 and USP28 can mediate p53 activation and p21-dependent cell cycle arrest [119]."
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"Multiple studies indicate that P53 is a downstream target protein of USP28, as USP28 can stabilize and activate P53 [ xref , xref , xref , xref – xref ]."
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"Understanding how 53BP1 and USP28 elevate p53 in response to centrosome loss and extended mitotic duration, and determining whether centrosome loss is an independent input into the p53 circuit or triggers p53 elevation because it leads to sequential prolonged mitoses, are important future goals arising from the results described here."
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"Knockout of 53BP1 or USP28 prevents the stabilization of P53 in cells that experience prolonged mitosis, indicating that 53BP1 and USP28 lie upstream of P53 in this signaling axis (Fong et al. 2016; Lambrus et al. 2016; Meitinger et al. 2016)."
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"A genome-wide CRISPR/Cas9 screen of centrinone-treated cells revealed that depletion of TP53BP1, USP28, or TRIM37 inhibits p53 elevation and alleviates proliferation arrest upon centrosome loss [ 41 ][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"USP28 depletion decreased p53 protein, but not p53 transcript, levels in BJ cells undergoing replicative senescence (Fig. 2E; Supplemental Fig. S3E,F)."
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"53BP1 responds to mitotic stress, which prolongs mitosis, or to DNA damage and triggers the stabilization of p53 by the deubiquitinase USP28 to stop the proliferation of potentially damaged cells."
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"USP28 overexpression increased the levels of multiple senescence markers, including p53, p21 , and GATA4 proteins but not p16, again suggesting that USP28 may be inducing senescence in part through the p53 and GATA4 branches (Fig. 3C–E; Supplemental Fig. S3K,L)."
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"XREF_BIBR Intriguingly, 53BP1 and USP28 mediated p53 dependent cell cycle arrest in response to centrosome loss and prolonged mitosis."
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"Furthermore, knockout of USP28 prevented P53 up-regulation, consistent with the notion that P53 activation in these microcephaly models occurs through MSP signaling."
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USP28 activates mutated TP53. 1 / 1
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"Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization."
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USP28 binds TP53.
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USP28 binds TP53. 10 / 22
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"Structural and functional analysis further implicated the BRCT domains of 53BP1 in mediating interactions with both p53 and USP28 to transcriptionally activate p53-target genes and the G1/S checkpoint independently of DNA repair."
39398482
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"The authors found that Polo‐like kinase 1 (PLK1) promotes stopwatch complex formation by phosphorylating 53BP1, which then can bind to p53 and USP28."
40884189
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"53BP1 controls p53-dependent responses through direct binding of p53 and USP28 ( xref ) and promotes NHEJ-mediated DSB repair by inhibiting DNA end resection ( xref ; xref )."
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"53BP1 controls p53-dependent responses through direct binding of p53 and USP28 (Cuella-Martin et al., 2016) and promotes NHEJ-mediated DSB repair by inhibiting DNA end resection (Panier and Boulton, 2013; Setiaputra and Durocher, 2019)."
33606978
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"This hypothesis is further supported by biochemical work showing that both p53 and USP28 interact with the tandem-BRCT domains of 53BP1 [ xref – xref ], which are dispensable for the DNA damage response role of 53BP1 [ xref ], but are required for the centrosome surveillance pathway [ xref ]."
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"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 ( xref ; xref )."
39398482
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"Furthermore, USP28 and p53 bind the BRCT repeats at different interfaces, and it has been shown that 53BP1 and USP28 share a co-regulatory role in supporting p53 functions [ xref ] ( xref )."
28188027
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"53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain-mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28."
27546791
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"Cuella-Martin et al. show that 53BP1 bridges interactions between p53 and the deubiquitinating enzyme USP28, promoting p53-DNA interactions to globally enhance p53-dependent transcriptional programs."
27546791
sparser
"Here, 53BP1’s C-terminal BRCT domains bridge p53’s interaction with the deubiquitinating enzyme USP28, catalysing de-ubiquitination events that stimulate p53 binding to, and activation of, target gene promoters xref ."
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TP53BP1 binds USP28 and TP53. 8 / 8
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"In line with our transcriptomic analyses ( xref ), our data collectively reveal a function for 53BP1-dependent bivalent interactions with USP28 and p53 in enhancing p53-promoter element interactions, thereby amplifying p53-dependent transcriptional programs."
27546791
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"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
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"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."
27432896
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"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."
27546791
sparser
"To determine whether V1544, G1560 and/or G1593 regulate the interaction of 53BP1 with p53 and/or USP28, we immunoprecipitated HA-tagged 53BP1 WT and mutant protein complexes from HEK293T cells ( xref )."
33606978
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"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 , xref ( xref )."
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"These data show that 53BP1 binds independently to p53 and USP28 via distinct BRCT domain surfaces and pointed toward a potential cooperative role for USP28-53BP1 complexes in p53 regulation."
27546791
sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
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CDKN1A binds TP53, TP53BP1, and USP28. 1 / 1
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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 xref )."
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CHEK2 binds TP53, MYC, E3_Ub_ligase, and USP28. 1 / 1
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"Another potential candidate is UBR5, an E3 ligase that interacts with several reported USP28 substrates such as CHK2, p53, and c-MYC [ xref , xref , xref , xref ]."
| PMC
USP28 deubiquitinates TP53.
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USP28 deubiquitinates TP53. 10 / 11
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"However, USP28 also promotes tumour suppressive pathways, for example by deubiquitinating TP53, a function that is counteracted by nuclear caspase 8 during tumour relapse [5]."
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"Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo."
27371829
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"The nuclear p53 accumulation caused by overexpression of wild type USP28 was not due to a specific increase in p53 mRNA levels (XREF_FIG), further supporting our observation that USP28 deubiquitinates p53 for protein stabilization."
27371829
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"However, it was not clear whether USP28 deubiquitinates p53 to stabilize it or regulates its DNA binding function, or whether its impact on p53 is indirect, via other factors."
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"USP28 can directly deubiquitinate P53 and stabilize mutated P53, enhancing the ability of cancer cells to invade."
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"The signalling pathway involves 53BP1 and the deubiquitylase USP28 acting in a complex to deubiquitylate and stabilise p53, which in turn controls cell fate."
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"While 53BP1, USP28, and p53 have not yet been demonstrated to form a ternary complex, USP28 was able to deubiquitinate p53 in vitro [XREF_BIBR]."
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"Because 53BP1 is known to bind USP28 as well as p53, a possible scenario is that it bridges the two proteins so that USP28 can deubiquitinate p53, preventing the tumor suppressor from being targeted to the proteasome for degradation."
| PMC
ubibrowser
"its interacting protein <span class="match term0">USP28</span> that can directly deubiquitinate <span class="match term1">p53</span> in vitro and ectopically stabilize <span class="match term1">p53</span> in vivo"
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"They also observed that the deubiquitylase activity of USP28 was necessary to promote p53-dependent responses.Whether USP28 deubiquitylates p53 directly or modifies one of its coterie of binding prote[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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USP28 increases the amount of TP53.
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USP28 increases the amount of TP53. 1 / 1
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"Consistent with the lower expression of p53, p21 and p16, USP28-depleted 2BS cells had less blue-colored cells ( Fig. 6 C), and the numbers of senescence-positive cells in USP28 knockdown cells were a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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USP28 increases the amount of mutated TP53. 1 / 1
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"Moreover, we found that USP28 overexpression rescued mutant p53 levels in ΔFBXO42 or ΔCCDC6 RPE1 cells, indicating that USP28 is downstream of FBXO42/CCDC6 (Appendix Fig. 5D)."
38580884
USP28 inhibits TP53.
| 1
USP28 inhibits TP53. 1 / 1
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"Supporting this, tumor cells silenced for USP28 or 53BP1 have previously been shown to prevent p53 elevation and growth arrest in response to prolonged prometaphase in cancer cells with increased propensity of mitotic errors."
31982308
USP28 decreases the amount of TP53.
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USP28 decreases the amount of TP53. 1 / 1
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"Conversely, depletion of USP28 resulted in significantly increased K48 ubiquitination and simultaneously diminished p53 level, which could be fully reversed by addition of recombinant USP28 (XREF_FIG)."
31982308
TP53 affects USP28
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TP53 binds USP28.
2 | 3 27
USP28 binds TP53. 10 / 22
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"Structural and functional analysis further implicated the BRCT domains of 53BP1 in mediating interactions with both p53 and USP28 to transcriptionally activate p53-target genes and the G1/S checkpoint independently of DNA repair."
39398482
sparser
"The authors found that Polo‐like kinase 1 (PLK1) promotes stopwatch complex formation by phosphorylating 53BP1, which then can bind to p53 and USP28."
40884189
sparser
"53BP1 controls p53-dependent responses through direct binding of p53 and USP28 ( xref ) and promotes NHEJ-mediated DSB repair by inhibiting DNA end resection ( xref ; xref )."
33606978
reach
"53BP1 controls p53-dependent responses through direct binding of p53 and USP28 (Cuella-Martin et al., 2016) and promotes NHEJ-mediated DSB repair by inhibiting DNA end resection (Panier and Boulton, 2013; Setiaputra and Durocher, 2019)."
33606978
sparser
"This hypothesis is further supported by biochemical work showing that both p53 and USP28 interact with the tandem-BRCT domains of 53BP1 [ xref – xref ], which are dispensable for the DNA damage response role of 53BP1 [ xref ], but are required for the centrosome surveillance pathway [ xref ]."
28188027
sparser
"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 ( xref ; xref )."
39398482
sparser
"Furthermore, USP28 and p53 bind the BRCT repeats at different interfaces, and it has been shown that 53BP1 and USP28 share a co-regulatory role in supporting p53 functions [ xref ] ( xref )."
28188027
sparser
"53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain-mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28."
27546791
sparser
"Cuella-Martin et al. show that 53BP1 bridges interactions between p53 and the deubiquitinating enzyme USP28, promoting p53-DNA interactions to globally enhance p53-dependent transcriptional programs."
27546791
sparser
"Here, 53BP1’s C-terminal BRCT domains bridge p53’s interaction with the deubiquitinating enzyme USP28, catalysing de-ubiquitination events that stimulate p53 binding to, and activation of, target gene promoters xref ."
30559443
TP53BP1 binds USP28 and TP53. 8 / 8
| 8
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"In line with our transcriptomic analyses ( xref ), our data collectively reveal a function for 53BP1-dependent bivalent interactions with USP28 and p53 in enhancing p53-promoter element interactions, thereby amplifying p53-dependent transcriptional programs."
27546791
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
27371829
sparser
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."
27432896
sparser
"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."
27546791
sparser
"To determine whether V1544, G1560 and/or G1593 regulate the interaction of 53BP1 with p53 and/or USP28, we immunoprecipitated HA-tagged 53BP1 WT and mutant protein complexes from HEK293T cells ( xref )."
33606978
sparser
"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 , xref ( xref )."
29363672
sparser
"These data show that 53BP1 binds independently to p53 and USP28 via distinct BRCT domain surfaces and pointed toward a potential cooperative role for USP28-53BP1 complexes in p53 regulation."
27546791
sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
28188027
CDKN1A binds TP53, TP53BP1, and USP28. 1 / 1
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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 xref )."
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CHEK2 binds TP53, MYC, E3_Ub_ligase, and USP28. 1 / 1
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"Another potential candidate is UBR5, an E3 ligase that interacts with several reported USP28 substrates such as CHK2, p53, and c-MYC [ xref , xref , xref , xref ]."
| PMC
TP53 activates USP28.
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TP53 activates USP28. 3 / 3
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"In 2 out of 3 cell line screens, the fitness attenuation effect of TP53-/- background cells was stronger in USP28 than in the neighboring ATM gene, supporting the causal role of USP28 in that segment (Additional file 3: Data S5)."
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"Moreover, purified USP28 was found to directly deubiquitinate p53 in vitro (XREF_FIG), raising potentially a direct role of USP28 in stabilizing p53 in vivo."
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"Homozygosity of either Usp28 or 53bp1 loss reduced p53 activation and rescued brain size in both Sas4 and Cep63 microcephaly models ( xref )."
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TP53 inhibits USP28.
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TP53 inhibits USP28. 1 / 1
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"P53 negatively regulates USP28, which may explain p53's known feedback role in attenuating SASP (Coppe et al. 2008), much like miR146a's role in attenuating NF-κB signaling (Bhaumik et al. 2009)."
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