HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53

Mi Huang, Duanzhuo Li, Yuwen Huang, Xiukun Cui, Shengjie Liao, Jiuxiang Wang, Fei Liu, Chang Li, Meng Gao, Jiaxiang Chen, Zhaohui Tang, David Wan Cheng Li, Mugen Liu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The differentiation from constantly dividing epithelial cells into secondary fiber cells is a key step during lens development. Failure in this process, which requires cell proliferation inhibition and cell cycle exit, causes cataract formation. HSF4 (Heat Shock Transcription Factor 4) gene mutations may lead to both congenital and senile cataract. However, how HSF4 mutations induce cataract formation remains obscure. In this study, we demonstrate that HSF4 can suppress the proliferation of human lens epithelial cells (HLECs) by promoting G1/S arrest in a p53-dependent manner. In contrast, HSF4 with cataract causative mutations fail to cause cell cycle arrest and have no obvious effect on cell proliferation. We further identify that HSF4 recruits p53 in the nucleus and promotes its transcriptional activity, leading to the expression of its target gene p21 in HLECs. HSF4, but not its cataract-causing mutants, stabilizes p53 protein and inhibits its ubiquitin degradation. Our data reveal that HSF4 may work as a switch between lens epithelial cell proliferation and secondary fiber cell differentiation, a process which mainly depends on p53. Through demonstration of this novel downstream pathway of HSF4, our results help uncover the pathogenic mechanisms caused by HSF4 mutations.

Original languageEnglish (US)
Pages (from-to)1808-1817
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

Lenses
Epithelial Cells
Cataract
Mutation
Cell Proliferation
heat shock transcription factor
Ubiquitin
Cell Cycle Checkpoints
Genes
Cell Differentiation
Cell Cycle

Keywords

  • Cataract
  • Cell cycle arrest
  • GAPDH
  • GFP
  • GST
  • HSF4
  • P53 stability
  • Proliferation
  • QPCR
  • RNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53. / Huang, Mi; Li, Duanzhuo; Huang, Yuwen; Cui, Xiukun; Liao, Shengjie; Wang, Jiuxiang; Liu, Fei; Li, Chang; Gao, Meng; Chen, Jiaxiang; Tang, Zhaohui; Li, David Wan Cheng; Liu, Mugen.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1853, No. 8, 01.08.2015, p. 1808-1817.

Research output: Contribution to journalArticle

Huang, M, Li, D, Huang, Y, Cui, X, Liao, S, Wang, J, Liu, F, Li, C, Gao, M, Chen, J, Tang, Z, Li, DWC & Liu, M 2015, 'HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53', Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1853, no. 8, pp. 1808-1817. https://doi.org/10.1016/j.bbamcr.2015.04.018
Huang, Mi ; Li, Duanzhuo ; Huang, Yuwen ; Cui, Xiukun ; Liao, Shengjie ; Wang, Jiuxiang ; Liu, Fei ; Li, Chang ; Gao, Meng ; Chen, Jiaxiang ; Tang, Zhaohui ; Li, David Wan Cheng ; Liu, Mugen. / HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2015 ; Vol. 1853, No. 8. pp. 1808-1817.
@article{0ddbc727225244879dfa500d597f17d5,
title = "HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53",
abstract = "The differentiation from constantly dividing epithelial cells into secondary fiber cells is a key step during lens development. Failure in this process, which requires cell proliferation inhibition and cell cycle exit, causes cataract formation. HSF4 (Heat Shock Transcription Factor 4) gene mutations may lead to both congenital and senile cataract. However, how HSF4 mutations induce cataract formation remains obscure. In this study, we demonstrate that HSF4 can suppress the proliferation of human lens epithelial cells (HLECs) by promoting G1/S arrest in a p53-dependent manner. In contrast, HSF4 with cataract causative mutations fail to cause cell cycle arrest and have no obvious effect on cell proliferation. We further identify that HSF4 recruits p53 in the nucleus and promotes its transcriptional activity, leading to the expression of its target gene p21 in HLECs. HSF4, but not its cataract-causing mutants, stabilizes p53 protein and inhibits its ubiquitin degradation. Our data reveal that HSF4 may work as a switch between lens epithelial cell proliferation and secondary fiber cell differentiation, a process which mainly depends on p53. Through demonstration of this novel downstream pathway of HSF4, our results help uncover the pathogenic mechanisms caused by HSF4 mutations.",
keywords = "Cataract, Cell cycle arrest, GAPDH, GFP, GST, HSF4, P53 stability, Proliferation, QPCR, RNA",
author = "Mi Huang and Duanzhuo Li and Yuwen Huang and Xiukun Cui and Shengjie Liao and Jiuxiang Wang and Fei Liu and Chang Li and Meng Gao and Jiaxiang Chen and Zhaohui Tang and Li, {David Wan Cheng} and Mugen Liu",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.bbamcr.2015.04.018",
language = "English (US)",
volume = "1853",
pages = "1808--1817",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "8",

}

TY - JOUR

T1 - HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53

AU - Huang, Mi

AU - Li, Duanzhuo

AU - Huang, Yuwen

AU - Cui, Xiukun

AU - Liao, Shengjie

AU - Wang, Jiuxiang

AU - Liu, Fei

AU - Li, Chang

AU - Gao, Meng

AU - Chen, Jiaxiang

AU - Tang, Zhaohui

AU - Li, David Wan Cheng

AU - Liu, Mugen

PY - 2015/8/1

Y1 - 2015/8/1

N2 - The differentiation from constantly dividing epithelial cells into secondary fiber cells is a key step during lens development. Failure in this process, which requires cell proliferation inhibition and cell cycle exit, causes cataract formation. HSF4 (Heat Shock Transcription Factor 4) gene mutations may lead to both congenital and senile cataract. However, how HSF4 mutations induce cataract formation remains obscure. In this study, we demonstrate that HSF4 can suppress the proliferation of human lens epithelial cells (HLECs) by promoting G1/S arrest in a p53-dependent manner. In contrast, HSF4 with cataract causative mutations fail to cause cell cycle arrest and have no obvious effect on cell proliferation. We further identify that HSF4 recruits p53 in the nucleus and promotes its transcriptional activity, leading to the expression of its target gene p21 in HLECs. HSF4, but not its cataract-causing mutants, stabilizes p53 protein and inhibits its ubiquitin degradation. Our data reveal that HSF4 may work as a switch between lens epithelial cell proliferation and secondary fiber cell differentiation, a process which mainly depends on p53. Through demonstration of this novel downstream pathway of HSF4, our results help uncover the pathogenic mechanisms caused by HSF4 mutations.

AB - The differentiation from constantly dividing epithelial cells into secondary fiber cells is a key step during lens development. Failure in this process, which requires cell proliferation inhibition and cell cycle exit, causes cataract formation. HSF4 (Heat Shock Transcription Factor 4) gene mutations may lead to both congenital and senile cataract. However, how HSF4 mutations induce cataract formation remains obscure. In this study, we demonstrate that HSF4 can suppress the proliferation of human lens epithelial cells (HLECs) by promoting G1/S arrest in a p53-dependent manner. In contrast, HSF4 with cataract causative mutations fail to cause cell cycle arrest and have no obvious effect on cell proliferation. We further identify that HSF4 recruits p53 in the nucleus and promotes its transcriptional activity, leading to the expression of its target gene p21 in HLECs. HSF4, but not its cataract-causing mutants, stabilizes p53 protein and inhibits its ubiquitin degradation. Our data reveal that HSF4 may work as a switch between lens epithelial cell proliferation and secondary fiber cell differentiation, a process which mainly depends on p53. Through demonstration of this novel downstream pathway of HSF4, our results help uncover the pathogenic mechanisms caused by HSF4 mutations.

KW - Cataract

KW - Cell cycle arrest

KW - GAPDH

KW - GFP

KW - GST

KW - HSF4

KW - P53 stability

KW - Proliferation

KW - QPCR

KW - RNA

UR - http://www.scopus.com/inward/record.url?scp=84929190849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929190849&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2015.04.018

DO - 10.1016/j.bbamcr.2015.04.018

M3 - Article

VL - 1853

SP - 1808

EP - 1817

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 8

ER -