Premium
NAT 10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2
Author(s) -
Liu Xiaofeng,
Tan Yuqin,
Zhang Chunfeng,
Zhang Ying,
Zhang Liangliang,
Ren Pengwei,
Deng Hongkui,
Luo Jianyuan,
Ke Yang,
Du Xiaojuan
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540505
Subject(s) - biology , microbiology and biotechnology , nat , mdm2 , genetics , apoptosis , computer network , computer science
As a genome guardian, p53 maintains genome stability by arresting cells for damage repair or inducing cell apoptosis to eliminate the damaged cells in stress response. Several nucleolar proteins stabilize p53 by interfering Mdm2–p53 interaction upon cellular stress, while other mechanisms by which nucleolar proteins activate p53 remain to be determined. Here, we identify NAT 10 as a novel regulator for p53 activation. NAT 10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT 10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. After DNA damage, NAT 10 translocates to nucleoplasm and activates p53‐mediated cell cycle control and apoptosis. Finally, NAT 10 inhibits cell proliferation and expression of NAT 10 decreases in human colorectal carcinomas. Thus, our data demonstrate that NAT 10 plays a critical role in p53 activation via acetylating p53 and counteracting Mdm2 action, providing a novel pathway by which nucleolar protein activates p53 as a cellular stress sensor.