The human papillomavirus type 16 E7 oncoprotein targets Myc-interacting zinc-finger protein-1

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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. © 2011 Elsevier Inc.

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APA

Morandell, D., Kaiser, A., Herold, S., Rostek, U., Lechner, S., Mitterberger, M. C., … Zwerschke, W. (2012). The human papillomavirus type 16 E7 oncoprotein targets Myc-interacting zinc-finger protein-1. Virology, 422(2), 242–253. https://doi.org/10.1016/j.virol.2011.10.027

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