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Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress.
Choi, Soo-Youn; Jang, Hyonchol; Roe, Jae-Seok; Kim, Seong-Tae; Cho, Eun-Jung; Youn, Hong-Duk.
Afiliação
  • Choi SY; Department of Biomedical Sciences, Department of Biochemistry and Molecular Biology, National Creative Research Center for Epigenome Reprogramming Network, Seoul, Republic of Korea.
Nucleic Acids Res ; 41(4): 2180-90, 2013 Feb 01.
Article em En | MEDLINE | ID: mdl-23303793
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dano ao DNA / Ativação Transcricional / Proteína Supressora de Tumor p53 / Proteínas Adaptadoras de Transdução de Sinal / Ubiquitinação Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dano ao DNA / Ativação Transcricional / Proteína Supressora de Tumor p53 / Proteínas Adaptadoras de Transdução de Sinal / Ubiquitinação Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article