Molecular mechanism of carcinogenesis by human papillomavirus-16.
Human papillomaviruses (HPVs) are common DNA viruses in humans. Recently, epithelial cancers associated with HPV infection have been used as models of virus-induced carcinogenesis. HPVs can be divided into two groups, mucosal and cutaneous. HPV-16 is the most frequent mucosal type associated with cervical cancer. Although the molecular mechanisms of carcinogenesis by HPV-16 have not been completely elucidated, it is apparent that HPV infection is the major risk factor in cervical carcinogenesis. Two viral early genes, E6 and E7, and an upstream regulatory region (URR) are preserved in cervical carcinoma cell lines as well as in clinical samples of cervical cancer, indicating that these regions are important in cancer development. E6 and E7 function as transforming genes. E6 protein binds to and promotes degradation of the tumor suppressor protein, p53, while E7 protein complexes and inactivates the Rb protein; together, they disrupt cell cycle regulation. E6 and E7 are transcribed from a promoter, P97. P97 is regulated by complex interactions between multiple, positive and negative, cellular factors and the viral E2 product. E2 disruption caused by the integration into the cellular genome may induce overexpression of E6 and E7. The E6 and E7 proteins are thought to act as critical factors in cervical carcinogenesis by inactivating the two tumor suppressor proteins, p53 and Rb, which are commonly mutated in other human cancers.
Ishiji
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Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan.
D002277:Carcinoma / Q000821:virology*; D002453:Cell Cycle / Q000235:genetics; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D016335:Zinc Fingers / Q000235:genetics
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D011505:Protein-Tyrosine Kinases