Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress

被引：21

作者：

Choi, Soo-Youn ^{[1
,2
]}

Jang, Hyonchol ^{[1
,2
]}

Roe, Jae-Seok ^{[1
,2
]}

Kim, Seong-Tae ^{[3
]}

Cho, Eun-Jung ^{[4
]}

Youn, Hong-Duk ^{[1
,2
,5
]}

机构：

[1] Seoul Natl Univ, Coll Med, Natl Creat Res Ctr Epigenome Reprogramming Networ, Dept Biomed Sci, Seoul 110799, South Korea

[2] Seoul Natl Univ, Coll Med, Natl Creat Res Ctr Epigenome Reprogramming Networ, Dept Biochem & Mol Biol, Seoul 110799, South Korea

[3] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon 440746, South Korea

[4] Sungkyunkwan Univ, Coll Pharm, Natl Res Lab Chromatin Dynam, Suwon 440746, South Korea

[5] Seoul Natl Univ, Grad Sch Convergence & Technol, WCU Dept Mol Med & Biopharmaceut Sci, Seoul 110799, South Korea

来源：

NUCLEIC ACIDS RESEARCH | 2013年 / 41卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

NUCLEOTIDE EXCISION-REPAIR; DNA-DAMAGE RECOGNITION; HIPPEL-LINDAU PROTEIN; PIGMENTOSUM GROUP-E; ATM; LIGASE; ACTIVATION; CHROMATIN; COMPLEX; KINASE;

D O I：

10.1093/nar/gks1319

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2180 / 2190

页数：11

共 37 条

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