title: Cancerous inhibitor of protein phosphatase 2A contributes to human papillomavirus oncoprotein E7-induced cell proliferation via E2F1.
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that is overexpressed in many human malignant tumors including cervical cancer. Human papillomavirus (HPV) oncoprotein E7 is the key transformation factor in cervical cancer. Our previous data showed a positive association of CIP2A and HPV-16E7 protein levels; however, how CIP2A is regulated by HPV-E7 and the roles of CIP2A in HPV-E7-mediated cell proliferation are unknown. In this study, we demonstrated that HPV-16E7 protein significantly upregulating CIP2A mRNA and protein expression depended on retinoblastoma protein pRb rather than p130. CIP2A siRNA knockdown in HPV-E7-expressing cells inhibited cell proliferation, DNA synthesis and G1/S cell cycle progression. CIP2A siRNA decreased the protein levels of cyclin-dependent kinase 1 (Cdk1), Cdk2 and their partner cyclin A2, with no change in levels of Cdk4, Cdk6 and their partner cyclin D1. The downregulation of Cdk1 and Cdk2 was independent of c-Myc; instead, E2F1 was the main target of CIP2A in this process, as overexpression of E2F1 rescued the inhibitory effects of CIP2A siRNA knockdown on cell proliferation and G1 arrest of HPV-E7-expressing cells. Our studies reveal a novel function of CIP2A in HPV-16E7-mediated cell proliferation.
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Weifang
authors: W
authors: Zhang
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Hanxiang
authors: H
authors: Chen
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Yan
authors: Y
authors: Chen
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Juan
authors: J
authors: Liu
authors: Institute of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiao
authors: X
authors: Wang
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Xiuping
authors: X
authors: Yu
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.|Cancer Research Center, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Jason J
authors: JJ
authors: Chen
authors: Institute of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, China.
authors: Weiming
authors: W
authors: Zhao
mesh_terms: D017209:Apoptosis; D001324:Autoantigens / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D010766:Phosphorylation; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein
keywords: CIP2A; E2F1; E7; G1 arrest; HPV
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