title: Degradation of p53 by natural variants of the E6 protein of human papillomavirus             type 16.
abstract: The degradation of p53 by high-risk human papillomavirus (HR-HPV) E6 proteins             is recognized as necessary for the immortalization of mammary epithelial cells             and the progression of cancer. The HR-HPV type 16 E6 proteins exhibit numerous             variants associated with different risk factors for the development of cervical             cancer. Two variants of E6 proteins, D25E and L83V, are common in cervical carcinomas             among Asian and European populations. In the present study, we compared the effect             of two E6 variants on p53 degradation by a prototype E6 protein. We demonstrate             that both the D25E and L83V variants downregulate p53 through a ubiquitin-proteasome             pathway, and that the effect is very similar to that of the prototype E6 protein.             The reduction in the p53 protein levels was induced through the ubiquitin-proteasome             pathway via interaction with E6 proteins. The expression of p21 CIP1/WAF1, a downstream             molecule of p53, was similarly reduced in both prototype and variant E6 protein-expressing             cell lines, leading to aberrant G1/S cell cycle arrest. These results suggest             that the natural variants, E6 D25E and L83V, similar to the prototype E6 protein,             contribute to tumorigenesis by degrading p53.
authors: Division of AIDS, Center for Immunology and Pathology, Korea                     National Institute of Health, Seoul, Republic of Korea.
authors: Ja Woon
authors: JW
authors: Yi
authors: Mi
authors: M
authors: Jang
authors: Sung Jin
authors: SJ
authors: Kim
authors: Sung Soon
authors: SS
authors: Kim
authors: Jee Eun
authors: JE
authors: Rhee
mesh_terms: D059447:Cell Cycle Checkpoints; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex