[Mechanisms of high-risk human papillomavirus-induced cervical carcinogenesis].
Human papillomaviruses (HPVs) are believed to be the primary causal agents for development of pre-neoplastic and malignant lesions of the uterine cervix and high-risk types such as type 16 and 18 are associated with more than 90% of all cervical carcinomas. The E6 and E7 genes of HPVs are thought to play causative roles, since E6 promotes the degradation of p53 through its interaction with E6AP, an E3 ubiquitin ligase, whereas E7 binds to the retinoblastoma protein pRb and disrupts its complex formation with E2F transcription factors. Although prophylactic vaccines have become available, it is still necessary to clarify the mechanisms of HPV-induced carcinogenesis because of the widespread nature of HPV infection. In this article, the mechanisms of high-risk HPV E6 and E7-induced multistep carcinogenesis and recently identified functions of these oncoproteins are reviewed.
Narisawa-Saito
Mako
M
Virology Division, National Cancer Center Research Institute, Tokyo.
Kiyono
Tohru
T
D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005260:Female; D016158:Genes, p53; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000472:pathogenicity*; D052161:Human papillomavirus 18 / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D012306:Risk; D044767:Ubiquitin-Protein Ligases; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology*
D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D044767:Ubiquitin-Protein Ligases