IndraLab

Statements

USP28 affects TP53
1 | 3 31 26
USP28 binds TP53.
| 2 24
TP53 binds USP28. 10 / 14
| 2 12
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
"The 53BP1 BRCT Domain Mediates Bivalent Interactions with p53 and USP28."
27546791
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
"Interestingly, the tandem BRCT domain is known to interact with p53 and USP28 ( xref ; xref ; xref ; xref )."
27371829
sparser
"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
sparser
"Thus, our data identify an important role for 53BP1-bridged p53-USP28 interaction in regulating p53 function in human cells."
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
reach
"This would be consistent with a putative cooperation between p53, 53BP1, and USP28 in tumor suppression."
27546791
sparser
"Furthermore, USP28 and p53 bind the BRCT repeats at different interfaces, and it has been shown that 53BP1 and USP28 share a coregulatory role in supporting p53 functions [20] ( Figure 1 B,C)."
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
TP53 binds TP53BP1 and USP28. 9 / 9
| 9
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
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."
27432896
sparser
"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
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [14,19] ."
28188027
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
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
28188027
sparser
"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."
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
"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
TP53 binds TP53BP1, USP28, and CDKN1A. 2 / 2
| 2
sparser
"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 s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28188027
sparser
"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 )."
28188027
E3_Ub_ligase binds TP53, USP28, CHEK2, and MYC. 1 / 1
| 1
sparser
"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 activates TP53.
| 3 19 2
USP28 activates TP53. 10 / 24
| 3 19 2
eidos
"Following p53 localization under such conditions , 53BP1 and USP28 can mediate p53 activation and p21-dependent cell cycle arrest [ 119 ] ."
31861395
reach
"53BP1 and USP28 mediate p53 dependent cell cycle arrest in response to centrosome loss and prolonged mitosis."
27371829
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"53BP1 and USP28 somehow measure mitotic duration and activate p53 upon mitotic exit."
28249963
reach
"Loss of 53BP1, USP28, and TRIM37 all prevented p53 stabilization and G1 arrest following centrosome loss."
28188027
sparser
"Previous reports showed that 53BP1 and USP28 activate p53, preventing the proliferation of cells that have an increased chance of mitotic errors [ xref ]."
| PMC
reach
"Knockout of USP28 did not alter basal levels of p53 or prevent p53 stabilization in response to doxorubicin induced DNA damage (XREF_FIG and Fig."
27432896
eidos
"USP28Delta cells were used as the control because inactivation of USP28 prevents p53 activation and G1 arrest that is observed as a consequence of delayed mitosis following centrosome loss in RPE1 cells13 ."
32908304
reach
"Following p53 localization under such conditions, 53BP1 and USP28 can mediate p53 activation and p21-dependent cell cycle arrest [119]."
31861395
reach
"Previous reports showed that 53BP1 and USP28 activate p53, preventing the proliferation of cells that have an increased chance of mitotic errors [104]."
| PMC
reach
"Deletion of TP53BP1, USP28, or TRIM37 prevented p53 elevation in response to centrosome loss but did not affect cytokinesis failure induced arrest or p53 elevation after doxorubicin induced DNA damage."
27432897
USP28 deubiquitinates TP53.
1 | 7
USP28 deubiquitinates TP53. 8 / 8
1 | 7
reach
"While 53BP1, USP28, and p53 have not yet been demonstrated to form a ternary complex, USP28 was able to deubiquitinate p53 in vitro [9]."
28188027
reach
"The signalling pathway involves 53BP1 and the deubiquitylase USP28 acting in a complex to deubiquitylate and stabilise p53, which in turn controls cell fate."
28900014
reach
"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
reach
"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."
33961797
reach
"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]."
28188027
reach
"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
ubibrowser
"its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo"
27371829
reach
"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
USP28 decreases the amount of TP53.
| 2
USP28 decreases the amount of TP53. 2 / 2
| 2
reach
"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
reach
"Notably, USP28 knockdown cells had decreased expression of p53, p21 and p16 INK4a, suggesting that the effect of USP28 on cell proliferation was mediated by regulating the expression of p53, p21 and p16 INK4a."
30910399
USP28 inhibits TP53.
| 1
USP28 inhibits TP53. 1 / 1
| 1
reach
"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
TP53 affects USP28
| 3 24
TP53 binds USP28.
| 2 24
TP53 binds USP28. 10 / 14
| 2 12
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
"The 53BP1 BRCT Domain Mediates Bivalent Interactions with p53 and USP28."
27546791
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
"Interestingly, the tandem BRCT domain is known to interact with p53 and USP28 ( xref ; xref ; xref ; xref )."
27371829
sparser
"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
sparser
"Thus, our data identify an important role for 53BP1-bridged p53-USP28 interaction in regulating p53 function in human cells."
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
reach
"This would be consistent with a putative cooperation between p53, 53BP1, and USP28 in tumor suppression."
27546791
sparser
"Furthermore, USP28 and p53 bind the BRCT repeats at different interfaces, and it has been shown that 53BP1 and USP28 share a coregulatory role in supporting p53 functions [20] ( Figure 1 B,C)."
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
TP53 binds TP53BP1 and USP28. 9 / 9
| 9
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
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."
27432896
sparser
"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
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [14,19] ."
28188027
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
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
28188027
sparser
"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."
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
"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
TP53 binds TP53BP1, USP28, and CDKN1A. 2 / 2
| 2
sparser
"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 s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28188027
sparser
"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 )."
28188027
E3_Ub_ligase binds TP53, USP28, CHEK2, and MYC. 1 / 1
| 1
sparser
"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.
| 1
TP53 activates USP28. 1 / 1
| 1
reach
"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."
27371829