Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression

Fengfeng Cai; Ping Chen; Li Chen; Ewelina Biskup; Yan Liu; Pei-Chao Chen; Jian-Feng Chang; Wenjie Jiang; Yuanya Jing; Youwei Chen; Hui Jin; Su Chen

doi:10.1371/journal.pone.0113727

Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression

PLoS One. 2014 Nov 19;9(11):e113727. doi: 10.1371/journal.pone.0113727. eCollection 2014.

Authors

Fengfeng Cai¹, Ping Chen¹, Li Chen¹, Ewelina Biskup², Yan Liu³, Pei-Chao Chen⁴, Jian-Feng Chang¹, Wenjie Jiang¹, Yuanya Jing¹, Youwei Chen¹, Hui Jin⁵, Su Chen¹

Affiliations

¹ School of Life Sciences and Technology, Department of Breast Surgery of Yangpu Hospital, Research Center for Translational Medicine at East Hospital, Tongji University, Shanghai, P. R. China.
² Department of Oncology, University Hospital of Basel, Basel, Switzerland.
³ College of Life Sciences, Hebei United University, Tangshan, Hebei Province, P. R. China; The Cancer Institute, Tangshan People's Hospital, Tangshan, Hebei Province, P. R. China.
⁴ College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang Province, P. R. China.
⁵ Department of Biochemistry and Molecular Cell Biology, School of Medcine, Shanghai Jiao Tong University, Shanghai, P. R. China.

Abstract

Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Proliferation
Cyclin D1 / genetics
Cyclin D1 / metabolism*
G1 Phase
HeLa Cells
Histones / metabolism
Humans
Promoter Regions, Genetic
RNA Interference
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
S Phase
Transcription, Genetic
Ubiquitin-Conjugating Enzymes / antagonists & inhibitors
Ubiquitin-Conjugating Enzymes / genetics
Ubiquitin-Conjugating Enzymes / metabolism*
Ubiquitination
Up-Regulation

Substances

CCND1 protein, human
Histones
RNA, Messenger
RNA, Small Interfering
Cyclin D1
UBE2A protein, human
UBE2B protein, human
Ubiquitin-Conjugating Enzymes

Grants and funding

This work was supported by National Natural Science Foundation of China (Youth Program, #31201051, #31301148) and Shanghai Municipal Natural Science Foundation (General Program, #12ZR1433100, #12ZR1433000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.