Primary Appointment:
 Microbiology & Immunology

GEBS Cluster Affiliations:
 IMV - Immunology, Microbiology, and Virology

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester, New York 14642

Phone: (585) 275-3110
E-Mail: daksha_patel@urmc.rochester.edu

Human papillomavirus-16 genes involved in disruption of cell cycle control and differentiation

Human Papillomavirus 16 ( HPV16) genes disrupt the host cell pathways involved in cell cycle control and differentiation. In particular, HPV16 oncogenes E6 and E7 bind to various cellular factors and inhibit differentiation of epithelial cells, specifically keratinocytes (the virus's natural host). E7 has been shown to interact with the retinoblastoma tumour suppressor protein (Rb) as well as histone deacytylase (HDAC) complexes. E6 binds to, among, others, p53 and E6AP promoting early degradation of p53 and thus inhibiting its normal function in apoptosis.

We have recently shown that E6 can bind to transcription co-activators p300/CBP and suppress p300/CBP mediated transcriptional activation. Since E6 and E7 seem to have overlapping effects on cell cycle control and can together efficiently immortalize keratinocytes, it is likely that many more, as yet unidentified, genes are affected at the transcription level by the oncogenes. The focus of our research is to identify novel cellular factors whose expression is altered by E6 and E7 in differentiating keratinocytes. Presently we are in the process of isolating such genes by employing representational difference analysis (RDA).

Patel D, Incassati A, Wang N, McCance DJ. Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins. Cancer Res. 64:1299-306, 2004.

Roginskaya M, Connelly SM, Kim KS, Patel D, Dumont ME. Effects of mutations in the N terminal region of the yeast G protein alpha-subunit Gpa1p on signaling by pheromone receptors. Mol Genet Genomics. 271:237-48, 2004.

Patel D, Frelinger J, Goudsmit J, Kim B. A Novel in vitro Assay for Site-specific Proteases using Bead-attached GFP Substrate. BioTechniques 31:1194-98, 2001.

Patel D, Huang SH, Baglia LA, McCance DJ. The E6 protein of Human Papillomavirus Type 16 binds to and inhibits co-activation by CBP and p300. EMBO J. 18:5061-5072, 1999.