Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6141245 | Virology | 2012 | 12 Pages |
Abstract
We demonstrate that HPV-16 E7 forms a complex with Miz-1. UV-induced expression of the CDK-inhibitor p21Cip1 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 p21Cip1 and overcomes Miz-1-induced G1-phase arrest. The C-terminal E7Î79LEDLL83-mutant with reduced Miz-1-binding capacity was impaired in its capability to repress p21Cip1 expression; whereas the pRB-binding-deficient E7C24G-mutant inhibited p21Cip1 expression similar to wild-type E7. Using ChIP, we demonstrate that endogenous E7 is bound to the endogenous p21Cip1 core-promoter in CaSki cells and RNAi-mediated knock down of Miz-1 abrogates E7-binding to the p21Cip1 promoter. Co-expression of E7 with Miz-1 inhibited Miz-1-induced p21Cip1 expression from the minimal-promoter via Miz-1 DNA-binding sites. Co-expression of E7Î79LEDLL83 did not inhibit Miz-1-induced p21Cip1 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 p21Cip1 gene expression.
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Authors
Dieter Morandell, Andreas Kaiser, Steffi Herold, Ursula Rostek, Stefan Lechner, Maria C. Mitterberger, Pidder Jansen-Dürr, Martin Eilers, Werner Zwerschke,