MG132 plus apoptosis antigen-1 (APO-1) antibody cooperate to restore p53 activity inducing autophagy and p53-dependent apoptosis in HPV16 E6-expressing keratinocytes

摘要: The E6 oncoprotein can interfere with the ability of infected cells to undergo programmed cell death through proteolytic degradation proapoptotic proteins such as p53, employing proteasome pathway. Therefore, inactivation MG132 should restore activity several proteins. We investigated whether in HPV16 E6-expressing keratinocytes (KE6 cells), restoration p53 levels mediated by and/or activation CD95 pathway apoptosis antigen-1 (APO-1) antibody are responsible for induction apoptosis. found that KE6 underwent mainly after incubation 24 h alone or APO-1 plus MG132. Both treatments activated extrinsic and intrinsic pathways. Autophagy was also activated, principally Inhibition E6-mediated proteasomal resulted elevation protein its phosphorylation Ser46 Ser20; localized at nucleus treatment In addition, transcriptional target genes p21, Bax TP53INP observed 3 6 treatment. Also, LC3 mRNA induced h, which correlates lipidation LC3B autophagy. Finally, using pifithrin alpha we a decrease MG132, suggesting sensitivity occurs part an increase both p53. use small molecules inhibit might permit death, providing new opportunities CC