title: The human papillomavirus type 16 E7 oncoprotein targets Myc-interacting zinc-finger protein-1.
abstract: We demonstrate that HPV-16 E7 forms a complex with Miz-1. UV-induced expression of the CDK-inhibitor p21(Cip1) and subsequent cell cycle arrest depends upon endogenous Miz-1 in HPV-negative C33A cervical cancer cells containing mutated p53. Transient expression of E7 in C33A inhibits UV-induced expression of p21(Cip1) and overcomes Miz-1-induced G1-phase arrest. The C-terminal E7Δ79LEDLL83-mutant with reduced Miz-1-binding capacity was impaired in its capability to repress p21(Cip1) expression; whereas the pRB-binding-deficient E7C24G-mutant inhibited p21(Cip1) expression similar to wild-type E7. Using ChIP, we demonstrate that endogenous E7 is bound to the endogenous p21(Cip1) core-promoter in CaSki cells and RNAi-mediated knock down of Miz-1 abrogates E7-binding to the p21(Cip1) promoter. Co-expression of E7 with Miz-1 inhibited Miz-1-induced p21(Cip1) expression from the minimal-promoter via Miz-1 DNA-binding sites. Co-expression of E7Δ79LEDLL83 did not inhibit Miz-1-induced p21(Cip1) expression. E7C24G retained E7-wild-type capability to inhibit Miz-1-dependent transactivation. These findings suggest that HPV-16 E7 can repress Miz-1-induced p21(Cip1) gene expression.
authors.affiliation: Cell Metabolism and Differentiation Research Group, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Morandell
authors.forename: Andreas
authors.initials: A
authors.lastname: Kaiser
authors.forename: Steffi
authors.initials: S
authors.lastname: Herold
authors.forename: Ursula
authors.initials: U
authors.lastname: Rostek
authors.forename: Stefan
authors.initials: S
authors.lastname: Lechner
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mitterberger
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.forename: Werner
authors.initials: W
authors.lastname: Zwerschke
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D051741:Kruppel-Like Transcription Factors; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C107961:ZBTB17 protein, human
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