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

doi:10.1093/nar/gks1319

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

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

20 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 language	English
Pages (from-to)	2180-2190
Number of pages	11
Journal	Nucleic acids research
Volume	41
Issue number	4
DOIs	https://doi.org/10.1093/nar/gks1319
Publication status	Published - 2013 Feb

Bibliographical note

Funding Information:
The National Creative Research Laboratory Program [2012R1A3A2048767 to H.-D.Y.]; Mid-Career Research Program, National Research Foundation of Korea [NRF-2007-0056786 and NRF-2010-0007646 to H.-D.Y.]; World Class University Program of the MEST and the NRF [R31-2008-000-10103-0]. Funding for open access charge: the National Creative Research Laboratory Program [2012R1A3A2048767].

All Science Journal Classification (ASJC) codes

Genetics

Access to Document

10.1093/nar/gks1319

Cite this

@article{1f35ea90b04c4033b4536b31bb2a0129,

title = "Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress",

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.",

author = "Choi, {Soo Youn} and Hyonchol Jang and Roe, {Jae Seok} and Kim, {Seong Tae} and Cho, {Eun Jung} and Youn, {Hong Duk}",

note = "Funding Information: The National Creative Research Laboratory Program [2012R1A3A2048767 to H.-D.Y.]; Mid-Career Research Program, National Research Foundation of Korea [NRF-2007-0056786 and NRF-2010-0007646 to H.-D.Y.]; World Class University Program of the MEST and the NRF [R31-2008-000-10103-0]. Funding for open access charge: the National Creative Research Laboratory Program [2012R1A3A2048767].",

year = "2013",

month = feb,

doi = "10.1093/nar/gks1319",

language = "English",

volume = "41",

pages = "2180--2190",

journal = "Nucleic acids research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Phosphorylation and ubiquitination-dependent degradation of CABIN1 releases p53 for transactivation upon genotoxic stress

AU - Choi, Soo Youn

AU - Jang, Hyonchol

AU - Roe, Jae Seok

AU - Kim, Seong Tae

AU - Cho, Eun Jung

AU - Youn, Hong Duk

N1 - Funding Information: The National Creative Research Laboratory Program [2012R1A3A2048767 to H.-D.Y.]; Mid-Career Research Program, National Research Foundation of Korea [NRF-2007-0056786 and NRF-2010-0007646 to H.-D.Y.]; World Class University Program of the MEST and the NRF [R31-2008-000-10103-0]. Funding for open access charge: the National Creative Research Laboratory Program [2012R1A3A2048767].

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84876396065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876396065&partnerID=8YFLogxK

U2 - 10.1093/nar/gks1319

DO - 10.1093/nar/gks1319

M3 - Article

C2 - 23303793

AN - SCOPUS:84876396065

SN - 0305-1048

VL - 41

SP - 2180

EP - 2190

JO - Nucleic acids research

JF - Nucleic acids research

IS - 4

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this