Direct activation of protein phosphatase‐2A0 by HIV‐1 encoded protein complex NCp7:vpr

Abstract
The effects of HIV‐1 encoded proteins NCp7, vpr and NCp7:vpr complex on the activity of protein phosphatase‐2A0 have been tested. We report that NCp7 is an activator of protein phosphatase‐2A0 and that vpr activated protein phosphatase‐2A0 only slightly. We also report that NCp7 and vpr form a tight complex which becomes a more potent activator of protein phosphatase‐2A0 than NCp7 alone. The ability of NCp7 to activate protein phosphatase‐2A0 is regulated by vpr. The C‐terminal portion of vpr prevents NCp7 from activating protein phosphatase‐2A0 while the N‐terminal portion of vpr potentiates the effect of NCp7 on the activity of protein phosphatase‐2A0. Our findings indicate that vpr may be acting as a targeting subunit which directs NCp7 to activate protein phosphatase‐2A0. In view of the fact that protein phosphatase‐2A functions as an inhibitor of G2 to M transition of the cell cycle and is involved in other key cellular processes such as the control of RNA transcription, the results presented in this report may explain how HIV‐1 causes cell cycle arrest which may lead to CD4+ T cell depletion and also how it disturbs normal cellular processes of its host cell.