J. Virol., 11 1996, 7535-7539, Vol 70, No. 11
Copyright © 1996, American Society for Microbiology

Human papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes

YP Tsao, LY Li, TC Tsai and SL Chen
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Here we report that the E5 proteins of human papillomavirus type 11 (HPV-11) and HPV-16 suppressed the expression of the p21(WafI/SdiI/CipI) tumor suppressor gene in NIH 3T3 cells and immortalized human keratinocytes. The promoter activity of p21 was repressed by E5 of HPV-11 and -16, suggesting that p21 gene suppression by E5 was at the transcriptional level. Using an inducible system, we demonstrated that increased induction of HPV-11 E5 in NIH 3T3 cells and keratinocytes led to increased repression of p21 promoter activity. The repression of p21 promoter activity by a series of E5 mutants was somewhat correlated with their respective transforming activities. Previously, we and other investigators showed that the E5 proteins of HPV-11 and -16 can activate the expression of c-jun. The repression of p21 gene expression might be a mechanism of oncogene-mediated growth promotion, since the expression of c-jun also led to a reduction of the levels of p21 RNA and protein in keratinocytes. This is the first demonstration that E5 proteins of HPV-11 and -16 repress p21 gene expression, and this might be one of the mechanisms by which E5 stimulates cell proliferation. In addition, this is also the first report of c-jun repression of p21.

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