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J. Virol. doi:10.1128/JVI.02022-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The interaction of herpes simplex virus 1 regulatory protein ICP22 with the cdc25C phosphatase is enabled in vitro by viral protein kinases U_S3 and U_L13

Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, Illinois 60637

^* To whom correspondence should be addressed. Email: bernard.roizman{at}bsd.uchicago.edu.

	Abstract

Earlier studies have shown that ICP22 and the U_L13 protein kinase but not the U_S3 kinase are required for optimal expression of a subset of late (₂) genes exemplified by U_L38, U_L41 and U_S11. In primate cells ICP22 mediates the disappearance of inactive isoforms of cdc2, and degradation of the cyclins A and B1. The active cdc2 acquires a new partner, the viral DNA synthesis processivity factor U_L42. Cdc2-U_L42 complex recruits and phosphorylates topoisomerase II for efficient expression of the ₂ genes listed above. In uninfected cells the cdc25C phosphatase activates cdc2 by removing two inhibitory phosphates. The accompanying report shows in the absence of cdc25C, the rate of degradation of cyclin B1 is similar to that occurring in in infected wild-type mouse embryo fibroblast cells but the levels of cdc2 increased, and the accumulation of a subset of late proteins and virus yields are reduced. This report links ICP22 with cdc25C. We show that in infected cells ICP22 and U_S3 protein kinase mediate the phosphorylation of cdc25C at its C-terminal domain. In in vitro assays with purified components both U_L13 and U_S3 viral kinases phosphorylate cdc25C and ICP22. Cdc25C also interacts with cdc2. However in infected cells the ability of cdc25C to activate cdc2 by dephosphorylation of inactive cdc2 protein is reduced. Coupled with the phosphorylation of cdc25C by the U_S3 kinase, the results raise the possibility that HSV-1 diverts cdc25C to perform functions other than those performed in uninfected cells.

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