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

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 prom...

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Published in:PloS one 2014-11, Vol.9 (11), p.e113727-e113727
Main Authors: Cai, Fengfeng, Chen, Ping, Chen, Li, Biskup, Ewelina, Liu, Yan, Chen, Pei-Chao, Chang, Jian-Feng, Jiang, Wenjie, Jing, Yuanya, Chen, Youwei, Jin, Hui, Chen, Su
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Cancer
Cell cycle
Cell growth
Cell Line
Cell Proliferation
Cyclin D1
Cyclin D1 - genetics
Cyclin D1 - metabolism
Deoxyribonucleic acid
DNA
DNA damage
DNA methylation
DNA repair
Drosophila
Enzymes
G1 Phase
Genes
HeLa Cells
Histone H2B
Histones - metabolism
Humans
Insects
Life sciences
Medicine
Promoter Regions, Genetic
Proteins
RNA Interference
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
S Phase
Saccharomyces cerevisiae
Surgery
Transcription
Transcription, Genetic
Ubiquitin-conjugating enzyme
Ubiquitin-Conjugating Enzymes - antagonists & inhibitors
Ubiquitin-Conjugating Enzymes - genetics
Ubiquitin-Conjugating Enzymes - metabolism
Ubiquitination
Up-Regulation
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0113727