Activation of protein phosphatase-2A1 by HIV-1 Vpr Cell death causing peptide in intact CD4+ T cells and in vitro

✍ Scribed by Anwar Janoo; Peter W. Morrow; H.Y. Lim Tung

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 209 KB
• Volume: 94
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20347

✦ Synopsis

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 4þ T cells. HIV-1 Vpr 71-96 is a direct activator of protein phosphatase-2A 1 that has been purified from CD 4þ 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.