title: Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression.
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.
authors.affiliation: 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.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Oncology, University Hospital of Basel, Basel, Switzerland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Biskup
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang Province, P. R. China.
authors.forename: Pei-Chao
authors.initials: PC
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Yuanya
authors.initials: Y
authors.lastname: Jing
authors.affiliation: 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.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medcine, Shanghai Jiao Tong University, Shanghai, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D006657:Histones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; C471545:UBE2A protein, human; C471546:UBE2B protein, human; D044763:Ubiquitin-Conjugating Enzymes