Functions of Human Papillomavirus Proteins
Cervical cancer is the second leading cause of deaths from cancer among women worldwide with approximately 500 000 deaths annually. Epidemiologic studies have implicated a sexually transmitted agent as a cause of cervical cancer, and molecular virology studies over the past 10 years have established a strong association between specific human papillomavirus (HPV) types and certain anogenital carcinomas, including cervical cancer (reviewed in zur Hausen and Schneider 1987). Over 65 different HPV types have now been described, and each is associated with a specific clinical entity (DeVilliers 1989). Approximately 20 or 25 HPVs have been associated with anogenital lesions; these HPVs have been further classified as either “low-risk” or “high-risk” types based on the preneoplastic character of the clinical lesions with which they are associated. Low-risk HPVs such as HPV-6 and HPV-11 are generally associated with venereal warts or condyloma acuminata which only rarely progress to malignancy. The high-risk HPVs include HPV-16 and HPV-18 and these are associated with squamous intraepithelial neoplasias which are potentially precancerous. In the cervix, they are associated with cervical intraepithelial neoplasia, or CIN. These CIN lesions are considered preneoplastic in that a small percentage of high-grade CIN lesions will progress to cervical cancer. Approximately 70% of human cervical cancers contain either HPV-16 or HPV-18 DNA (zur Hausen and Schneider 1987). Indeed, HPV-16 and HPV-18 DNA were originally isolated from human cervical carcinoma tissues (Dürst et al. 1983; Boshart et al. 1984). Other high-risk HPVs, including types 31, 33, 35, 39, 45, 51, and 52, have subsequently been identified and have also been associated with CIN lesions and with invasive cervical carcinomas. All together, approximately 85% of cervical cancers can be shown to contain DNA of one of the high-risk HPV types (Riou et al. 1990).
KeywordsZinc Glycine Serine Polypeptide Half Life
Unable to display preview. Download preview PDF.
- Chellappan S, Kraus VB, Kroger B, Münger K, Howley PM, Phelps WC, Nevins JR (1992) Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between the transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci USA 89:4549–4553.PubMedCrossRefGoogle Scholar
- Cripe TP, Haugen TH, Turk JP, Tabatabai F, Schmid PG, Durst M, Gissmann L, Roman A, Turek LP (1987) Transcriptional regulation of the human papillomavirus-16 E6–E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO J 6:3745–3753.PubMedGoogle Scholar
- DeVilliers, EM (1989) Heterogeneity of the human papillomavirus group. J Virol 63:4898–4903.Google Scholar
- Matlashewski G, Schneider J, Banks L, Jones N, Murray A, Crawford L (1987) Human papillomavirus type 16 DNA co-operates with activated ras in transforming primary cells. EMBO J 6:1141–1146.Google Scholar
- Reich NC, Oren M, Levine AJ (1983) Two distinct mechanisms regulate the levels of a cellular tumor antigen. Mol Cell Biol 3:2134–2150.Google Scholar
- Sandler AB, Vande Pol SB, Spalholz BS (1993) Repression of BPV-1 transcription by the E1 replication protein. J Virol 67: (in press).Google Scholar
- Scheffner M, Huibregtse JM, Vierstra RD, Howley PM (1993) The HPV-16 E6-AP complex functions as a ubiquitin-protein ligase in the ubiquination of p53. Cell 75 (in press).Google Scholar
- von Knebel-Doeberitz M, Oltersdorf T, Schwarz E, Gissmann L (1988) Correlation to modify human papillomavirus early gene expression with altered growth properties in C4-I cervical carcinoma cells. Cancer Res 48:3780–3785.Google Scholar
- zur Hausen H, Schneider A (1987) The role of papilloma-viruses in human anogenital cancers. In: Salzman N, Howley PM (eds) The papoviridae, vol 2: the papillomaviruses. Plenum, New York, pp 245–263.Google Scholar