Human papillomavirus type 11 and 16 E5 represses p21(WafI/SdiI/CipI) gene expression in fibroblasts and keratinocytes.
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.
Tsao
Y P
YP
Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Li
L Y
LY
Tsai
T C
TC
Chen
S L
SL
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014170:Transformation, Genetic; D000086082:Viroporin Proteins
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009856:Oncogene Proteins, Viral; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins