Activation of protein phosphatase-2A1 by HIV-1 Vpr cell death causing peptide in intact CD(4+) T cells and in vitro.
HIV-1, the etiologic agent of human AIDS, causes cell death in host and non-host cells via HIV-1 Vpr, one of its auxiliary gene product. HIV-1 Vpr can also cause cell cycle arrest in several cell types. The cellular processes that link HIV-1 Vpr to the cell death machinery are not well characterized. Here, we show that the C terminal portion of HIV-1 Vpr which encompasses amino acid residues 71-96 (HIV-1 Vpr(71-96)), also termed HIV-1 Vpr cell death causing peptide, is an activator of protein phosphatase-2A(1) when applied extracellularly to CD(4+) T cells. HIV-1 Vpr(71-96) is a direct activator of protein phosphatase-2A(1) that has been purified from CD(4+) T cells. Full length HIV-1 Vpr by itself does not cause the activation of protein phosphatase-2A(1) in vitro. HIV-1 Vpr(71-96) also causes the activation of protein phosphatase-2A(0) and protein phosphatase-2A(1) from brain, liver, and adipose tissues. These results indicate that HIV-1 can cause cell death of infected cells and non-infected host and non-host cells via HIV-1 Vpr derived C terminal peptide(s) which act(s) by cell penetration and targeting of a key controller of the cell death machinery, namely, protein phosphatase-2A(1). The activation of other members of the protein phosphatase-2A subfamily of enzymes which are involved in the control of several metabolic pathways in brain, liver, and adipose tissues by HIV-1 Vpr derived C terminal peptide(s) may underlie various metabolic disturbances that are associated with HIV-1 infection.
Janoo
Anwar
A
Protein and Nucleic Acids Chemistry Laboratory, Norchit Biomedical Research Institute, Liverpool (Syracuse) 13088, New York, NY, USA.
Morrow
Peter W
PW
Tung
H Y Lim
HY
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D016336:Gene Products, vpr / Q000378:metabolism* / Q000494:pharmacology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D054648:Protein Phosphatase 2; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D010446:Peptide Fragments; D054325:vpr Gene Products, Human Immunodeficiency Virus; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2