Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A

The Vpr protein of primate lentiviruses arrests cell cycling at the G(2)/M phase through an inactivation of cyclin B-p34(cdc2) and its upstream regula tor cdc25, We provide here biochemical and functional evidence demonstratin g that human immunodeficiency virus type 1 (HIV-1) Vpr mediates G(2) arrest by forming a complex with protein phosphatase 2A (PP2A), an upstream regul ator of cdc25, Vpr associates with PP2A through a specific interaction with the B55 regulatory subunit, This interaction is necessary but not sufficie nt for G(2) arrest. Interestingly, we found that Vpr association with B55-c ontaining PP2A targets the enzymatic complex to the nucleus and, importantl y, enhances the recruitment and dephosphorylation of the cdc25 substrate. O ur data suggest that Vpr mediates G(2) arrest by enhancing the nuclear impo rt of PP2A and by positively modulating its catalytic activity towards acti ve phosphorylated nuclear cdc25.