c-FLIPL regulates PKC via AP-2 to inhibit Bax-mediated apoptosis induced by HIV-1 gp120 in Jurkat cells.
c-FLIPL, an inhibitor of caspase 8, is known to inhibit the Fas/caspase 8 apoptotic pathway; however, its involvement of Bax/mitochondrial apoptosis is not well understood. Using human cells, Jurkat cell line, induced with HIV-1 gp120, we studied the effects of c-FLIPL on Bax/mitochondrial apoptosis. We found that the induction of apoptosis by HIV-1 envelope protein, gp120, involved the activation of both Bax-dependent and death receptor-mediated pathways, and HIV-1 infection deceased c-FLIPL expression. Interestingly, c-FLIPL expression downregulated protein kinase C (PKC) expression at the transcript level involving activated protein-2 (AP-2). c-FLIPL expression reduced AP-2 protein levels required to promote PKC protein expression and PKC-associated inactive form of Bax, and inhibited Bax activation, suggesting that c-FLIPL inhibits Bax activation via modulating PKC expression at the transcriptional level involving AP-2 during gp120 treatment. Collectively, these findings further corroborate the concept that gp120 plays an important role, via involvement of molecules such as c-FLIPL, in apoptotic cell death due to HIV-1 infection.
Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Building 29B, Rm 4NN16, 8800 Rockville Pike, Bethesda, MD, 20892, USA. xue.wang@fda.hhs.gov
Xue
X
Wang
Jiangqin
J
Zhao
Shixing
S
Tang
Sherwin
S
Lee
Robert I
RI
Glazer
Indira
I
Hewlett
D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000502:physiology*; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D006801:Humans; D019169:Jurkat Cells; D011493:Protein Kinase C / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D015699:HIV Envelope Protein gp120; D050656:Transcription Factor AP-2; D051028:bcl-2-Associated X Protein; D011493:Protein Kinase C