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

Soo Youn Choi, Hyonchol Jang, Jae Seok Roe, Seong Tae Kim, Eun Jung Cho, Hong Duk Youn

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2180-2190
Number of pages11
JournalNucleic acids research
Volume41
Issue number4
DOIs
Publication statusPublished - 2013 Feb 1

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Ubiquitination
Transcriptional Activation
DNA Damage
Phosphorylation
Ubiquitin
Phosphotransferases
Protein Stability
Ligases
Proteolysis
Chromatin
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Choi, Soo Youn ; Jang, Hyonchol ; Roe, Jae Seok ; Kim, Seong Tae ; Cho, Eun Jung ; Youn, Hong Duk. / Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress. In: Nucleic acids research. 2013 ; Vol. 41, No. 4. pp. 2180-2190.
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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.

In: Nucleic acids research, Vol. 41, No. 4, 01.02.2013, p. 2180-2190.

Research output: Contribution to journalArticle

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