Human immunodeficiency virus type 1 Vpr-mediated G2 cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A

AUTOR(ES)

Hrimech, Mohammed

FONTE

Oxford University Press

RESUMO

The Vpr protein of primate lentiviruses arrests cell cycling at the G2/M phase through an inactivation of cyclin B–p34cdc2 and its upstream regulator cdc25. We provide here biochemical and functional evidence demonstrating that human immunodeficiency virus type 1 (HIV-1) Vpr mediates G2 arrest by forming a complex with protein phosphatase 2A (PP2A), an upstream regulator of cdc25. Vpr associates with PP2A through a specific interaction with the B55 regulatory subunit. This interaction is necessary but not sufficient for G2 arrest. Interestingly, we found that Vpr association with B55-containing PP2A targets the enzymatic complex to the nucleus and, importantly, enhances the recruitment and dephosphorylation of the cdc25 substrate. Our data suggest that Vpr mediates G2 arrest by enhancing the nuclear import of PP2A and by positively modulating its catalytic activity towards active phosphorylated nuclear cdc25.

Documentos Relacionados

• Human Immunodeficiency Virus Type 1 Vpr-Mediated G2 Arrest Requires Rad17 and Hus1 and Induces Nuclear BRCA1 and γ-H2AX Focus Formation
• Characterization of a Hank’s Type Serine/Threonine Kinase and Serine/Threonine Phosphoprotein Phosphatase in Pseudomonas aeruginosa
• Cell Cycle- and Vpr-Mediated Regulation of Human Immunodeficiency Virus Type 1 Expression in Primary and Transformed T-Cell Lines
• Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in primate lentivirus evolution and biology.
• Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3