IndraLab

Statements


USP28 affects TP53BP1
7 1 1 | 28 42
USP28 binds TP53BP1.
7 1 | 23 41
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 )."
| 8

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

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
| 1

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.
| 3
USP28 activates TP53BP1. 3 / 3
| 3

reach
"USP28 mediates centrosome loss induced G1 arrest through its deubiquitinase activity, and acts downstream of 53BP1 to stabilize p53."

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
"However, USP28 loss did not strongly impair DDR signaling or DNA repair, consistent with previous work that found the 53BP1-BRCT domains were not required for the DNA repair functions of 53BP1(Figure 1A) (Knobel et al., 2014; Ward et al., 2006)."
USP28 inhibits TP53BP1.
| 1 1
| 1 1

sparser
"USP28 inhibits 53BP1 and maintains its assembly with PIKKS and its substrate complex, which promotes checkpoint activation and leads to cell cycle arrest [88] ."

reach
"USP28 inhibits 53BP1 and maintains its assembly with PIKKS and its substrate complex, which promotes checkpoint activation and leads to cell cycle arrest [88] ."
USP28 deubiquitinates TP53BP1.
1 | 1
USP28 deubiquitinates TP53BP1. 1 / 2
1 | 1

reach
"USP28 also modulates the DNA damage response (DDR) in cancer cells by deubiquitinating and stabilising the checkpoint kinase 2 (CHK2), the TP53-binding protein 1 (TP53BP1) and Claspin (CLSPN) [6, 7], thereby preventing apoptosis but establishing cell cycle arrest to facilitate DNA repair [8]."
TP53BP1 affects USP28
7 1 | 30 41
TP53BP1 binds USP28.
7 1 | 23 41
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 )."
| 8

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

sparser
"Previous work has shown that both p53 and USP28 directly interact with 53BP1 through its BRCT domains [ xref , xref ]."
| 1

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 activates USP28.
| 4
TP53BP1 activates USP28. 3 / 3
| 3

reach
"We show that USP28 dimerization is stimulated by 53BP1—the major binding partner of USP28 and a key mediator protein in cellular response to DNA damage and replicative stress (41,86–89)."

reach
"Depletion of 53BP1 in p19 Nras cells diminished USP28 dimerization (Figure 5C; Supplementary Figure S5E), mimicking the effect of etoposide."

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."
TP53BP1 bound to USP28 activates USP28. 1 / 1
| 1

reach
"USP28 dimerization is stimulated by 53BP1, which selectively binds USP28 dimers."
TP53BP1 inhibits USP28.
| 2
| 2

reach
"Incubation of total cell lysates with the Ub-VME/Ub-VS probes showed that depletion of 53BP1 stimulated USP28 deubiquitinase activity (Figure 5D, Supplementary Figure S5G), whereas the abundance of USP28 was not changed (Supplementary Figure S5H and I)."

reach
"We concluded that depletion of 53BP1 promotes formation of USP28 monomers and stabilizes MYC."
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."