Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
CABIN1 acts as a negative regulator of
p53
by keeping
p53
in an inactive state on chromatin. Genotoxic stress causes rapid dissociation of CABIN1 and activation of
p53
. However, its molecular mechanism is still unknown. Here, we reveal the phosphorylation- and ubiquitination-dependent degradation of CABIN1 upon DNA damage, releasing
p53
for transcriptional activation. The DNA-damage-signaling kinases, ATM and CHK2, phosphorylate CABIN1 and increase the degradation of
CABIN1 protein
. Knockdown or overexpression of these kinases influences the stability of
CABIN1 protein
showing that their activity is critical for degradation of CABIN1. Additionally, CABIN1 was found to undergo ubiquitin-dependent proteasomal degradation mediated by the CRL4DDB2 ubiquitin ligase complex. Both phosphorylation and ubiquitination of CABIN1 appear to be relevant for controlling the level of
CABIN1 protein
upon genotoxic stress.
...
PMID:Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress. 2330 93
