DIRECT ACTIVATION OF PROTEIN PHOSPHATASE-2A(0) BY HIV-1 ENCODED PROTEIN COMPLEX NCP7-VPR

The effects of HIV-1 encoded proteins NCp7, vpr and NCp7:vpr complex o n the activity of protein phosphatase-2A(0) have been tested, We repor t that NCp7 is an activator of protein phosphatase-2A(0) and that vpr activated protein phosphatase-2A(0) only slightly, We also report that NCp7 and vpr form a tight complex which becomes a more potent activat or of protein phosphatase-2A(0) than NCp7 alone, The ability of NCp7 t o activate protein phosphatase-2A(0) is regulated by vpr. The C-termin al portion of vpr prevents NCp7 from activating protein phosphatase-2A (0) while the N-terminal portion of vpr potentiates the effect of NCp7 on the activity of protein phosphatase-2A(0), Our findings indicate t hat vpr may be acting as a targeting subunit which directs NCp7 to act ivate protein phosphatase-2A(0), In view of the fact that protein phos phatase-2A functions as an inhibitor of G(0) to M transition of the ce ll cycle and is involved in other key cellular processes such as the c ontrol of RNA transcription, the results presented in this report may explain how HIV-1 causes cell cycle arrest which may lead to CD4+ T ce ll depletion and also how it disturbs normal cellular processes of its host cell.