0 28

Cited 0 times in

KLHL4, a novel p53 target gene, inhibits cell proliferation by activating p21 WAF/CDKN1A

Authors
 Seo-Hyun Choi  ;  Su-Yeon Cho  ;  Jiyang Song  ;  Man-Wook Hur 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.530(3) : 588-596, 2020-09 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2020-09
Keywords
Cell proliferation ; Cullin ; DNA damage ; KLHL4 ; Ubiquitination ; p21 ; p53
Abstract
KLHL4 is a member of the KLHL protein family, many of whom bind the Cul3 E3 ligase, and mediate the ubiquitination of interacting proteins. The KLHL4 gene, localized on the X chromosome, associates with a disorder known as X-linked cleft palate (CPX). However, the biological functions of KLHL4 are largely unknown. In this study, microarray analysis of HEK293A embryonic kidney cells, expressing ectopic p53, showed a 3-fold increase of KLHL4 mRNA. Moreover, both KLHL4 mRNA and protein expression were elevated by p53 or DNA damage, suggesting that KLHL4 might be a p53 target gene. We also found that KLHL4 activates transcription of p21WAF/CDKN1A, a p53 target gene encoding a major negative regulator of the cell-cycle. KLHL4 interacted with p53 to increase its binding to p53 response element of the p21WAF/CDKN1A gene, resulting in transcriptional upregulation. Furthermore, we observed that KLHL4 can interact with the Cul3 ubiquitin ligase, to possibly play a role in ubiquitin-mediated proteasomal degradation, and Klhl4 knocked-out MEF mouse embryonic fibroblasts proliferated faster than WT MEF cells. These results suggest that KLHL4 upregulation by p53 may inhibit cell proliferation, by activating p21WAF/CDKN1A.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X20314972
DOI
10.1016/j.bbrc.2020.07.100
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180231
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links