hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by   controlling NEDDylation of ribosomal protein S14

doi:10.1038/onc.2012.560

CORC > 北京大学 > 生命科学学院

	hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14
	Zhang, J. ; Bai, D. ; Ma, X. ; Guan, J. ; Zheng, X.
刊名	oncogene
	2014
关键词	hCINAP RPS14 NEDDylation HDM2 p53 SACCHAROMYCES-CEREVISIAE ADENYLATE KINASE P53 MDM2 INHIBITION HDM2 L11 IDENTIFICATION DEGRADATION ACTIVATION
DOI	10.1038/onc.2012.560
英文摘要	The tumor-suppressor p53 provides a critical brake on tumor development. HDM2 (human double-minute 2), a p53 E3 ubiquitin ligase, is the principal cellular antagonist of p53. Mounting evidence has suggested that ribosomal proteins (RPs) modulate HDM2-p53 as a novel pathway for regulating p53 signaling. However, the upstream regulators that mediate RP-HDM2-p53 circuits remain poorly understood. Here we identify human coilin-interacting nuclear ATPase protein (hCINAP) as an interacting partner of ribosomal protein S14 (RPS14). RPS14 stabilized and activated p53 by inhibiting HDM2-mediated p53 polyubiquitination and degradation. More importantly, RPS14 was specifically modified with NEDD8 and hCINAP inhibited RPS14 NEDDylation by recruiting NEDD8-specific protease 1. The decrease in RPS14 NEDDylation led to reduced stability and incorrect localization of RPS14, thereby attenuating the interaction between RPS14 and HDM2. Free HDM2 stimulated p53 polyubiquitination and degradation. In conclusion, we demonstrate that hCINAP acts as a novel regulator of RPS14-HDM2-p53 by regulating the interaction between RPS14 and HDM2 through the control of RPS14 NEDDylation. These findings suggest that hCINAP is an important regulator of RP-HDM2-p53 pathway and a potential anticancer drug target.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000329440700012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity; SCI(E); PubMed; 11; ARTICLE; xiaofengz@pku.edu.cn; 2; 246-254; 33
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/343068]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhang, J.,Bai, D.,Ma, X.,et al. hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14[J]. oncogene,2014.
APA	Zhang, J.,Bai, D.,Ma, X.,Guan, J.,&Zheng, X..(2014).hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14.oncogene.
MLA	Zhang, J.,et al."hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14".oncogene (2014).