Research ArticleVirology

Interference with the PTEN-MAST2 Interaction by a Viral Protein Leads to Cellular Relocalization of PTEN

Science Signaling  14 Aug 2012:
Vol. 5, Issue 237, pp. ra58
DOI: 10.1126/scisignal.2002941

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Rabies Virus Relocalizes PTEN

Virulent strains of rabies virus infect neurons and promote survival of the infected cells to favor viral replication. Among the host factors that inhibit neuronal survival are the phosphatase PTEN and one of its binding partners, the kinase MAST2. PTEN and MAST2 interact through the PDZ domain of MAST2 and the PDZ domain–binding site (PDZ-BS) of PTEN. Terrien et al. found that the rabies virus glycoprotein (G protein), which contains a PDZ-BS, disrupted the MAST2-PTEN complex in infected cells. Structural analysis showed that the surfaces of PTEN and G protein that interacted with MAST2 were similar and contained previously uncharacterized PDZ-binding regions. Finally, disruption of the MAST2-PTEN complex by viral G protein resulted in the relocalization of PTEN from the nucleus to the cytoplasm. Together, these data suggest that competition between viral G protein and MAST2 for binding to PTEN plays a role in the survival of infected cells.