Human papillomavirus type 77 E6 protein selectively inhibits p53-dependent transcription of proapoptotic genes following UV-B irradiation.
DNA damage, such as that elicited by UV-B, can induce either a cell cycle arrest or apoptosis that can be signalled by the p53 protein through the activation of a number of downstream cellular target genes. In contrast to oncogenic anogenital human papillomaviruses (HPVs), which mediate proteolytic degradation of p53, the E6 protein of cutaneous HPVs, such as HPV 77, do not promote p53 degradation. We have previously shown, however, that expression of HPV 77 E6 can effectively block UV-induced apoptosis in cells that have UV-activated p53. Here, we report that expression of the E6 protein from the cutaneous HPV 77 attenuates the UV-induced transactivation of p53-regulated proapoptotic genes Fas, PUMAbeta, Apaf-1, PIG3. This inhibition of p53-activation of proapoptotic genes by HPV77 E6 is exerted selectively, as the increased expression of p53 target genes involved in cell cycle arrest or regulatory functions regulation, such as p21 and Hdm2, is unaffected. Our data suggest that HPV 77 E6 may play an important role in specifically deregulating p53-dependent transactivation of proapoptotic genes upon UV-B irradiation.
Giampieri
Silvia
S
Cancer Research UK, Skin Tumour Laboratory, 2 Newark Street, London E1 2AT, UK.
García-Escudero
Ramon
R
Green
Judith
J
Storey
Alan
A
D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics
C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; C438378:BBC3 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C118860:E6 protein, Human papillomavirus type 6; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011506:Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D019014:fas Receptor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2