IndraLab

Statements


USP28 affects TP53BP1
5 1 1 | 14 22
USP28 binds TP53BP1.
5 1 | 12 22
5 1 | 12 10

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

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

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)."

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."

No evidence text available

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

sparser
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."

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."

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [14,19] ."

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 )."

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."

sparser
"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."

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 )."

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."
| 2

sparser
"Important future directions include dissecting the interactions between 53BP1 and USP28 that activate downstream p53p21 signaling as well as screening for the upstream components that transduce the s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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 )."
| 1

sparser
"Moreover, USP28 binds checkpoint proteins 53BP1, Claspin, and Mdc1 [ xref ]."
USP28 activates TP53BP1.
| 2
USP28 activates TP53BP1. 2 / 2
| 2

reach
"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."

reach
"USP28 mediates centrosome loss induced G1 arrest through its deubiquitinase activity, and acts downstream of 53BP1 to stabilize p53."
USP28 deubiquitinates TP53BP1.
1 |
USP28 deubiquitinates TP53BP1. 1 / 1
1 |
TP53BP1 affects USP28
5 1 | 14 22
TP53BP1 binds USP28.
5 1 | 12 22
5 1 | 12 10

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

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

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)."

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."

No evidence text available

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

sparser
"USP28 and p53 both bind to 53BP1 through the tandem C-terminal BRCT repeats ( xref ; xref )."

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."

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [14,19] ."

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 )."

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."

sparser
"We therefore hypothesize that 53BP1-USP28 complexes interact with nucleoplasmic p53 pools, where they function to prime p53 DNA-binding activity."

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 )."

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."
| 2

sparser
"Important future directions include dissecting the interactions between 53BP1 and USP28 that activate downstream p53p21 signaling as well as screening for the upstream components that transduce the s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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 )."
| 1

sparser
"Moreover, USP28 binds checkpoint proteins 53BP1, Claspin, and Mdc1 [ xref ]."
TP53BP1 deubiquitinates USP28.
| 1
TP53BP1 leads to the deubiquitination of USP28. 1 / 1
| 1

reach
"Mechanistically, as well as its role in DNA repair, 53BP1 promotes p53 signalling, by coordinating ubiquitin specific peptidase 28 (USP28)-mediated p53 deubiquitination."
TP53BP1 activates USP28.
| 1
TP53BP1 activates USP28. 1 / 1
| 1

reach
"Given that p53 activity is quenched via MDM2 dependent p53 ubiquitination, it is tempting to speculate that a 53BP1 dependent targeting of USP28 into p53 protein complexes might counteract such events."