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The Carboxyl-Terminal Domain of RNA Polymerase II Is Phosphorylated by a Complex Containing cdk9 and Infected-Cell Protein 22 of Herpes Simplex Virus 1

Authors
Publisher
American Society for Microbiology
Publication Date
Source
PMC
Keywords
  • Virus-Cell Interactions
Disciplines
  • Biology

Abstract

The infected-cell protein 22 (ICP22), a regulatory protein encoded by the α22 gene of herpes simplex virus 1, is required for the optimal expression of a set of late viral proteins that includes the products of the US11, UL38, and UL41 genes. ICP22 has two activities. Thus, ICP22 and the UL13 protein kinase mediate the activation of cdc2 and degradation of its partners, cyclins A and B. cdc2 and its new partner, the DNA polymerase accessory factor (UL42), bind topoisomerase IIα in an ICP22-dependent manner. In addition, ICP22 and UL13 mediate an intermediate phosphorylation of the carboxyl terminus of RNA polymerase II (RNA POL II). Here we report another function of ICP22. Thus, ICP22 physically interacts with cdk9, a constitutively active cyclin-dependent kinase involved in transcriptional regulation. A protein complex containing ICP22 and cdk9 phosphorylates in vitro the carboxyl-terminal domain of RNA POL II in a viral US3 protein kinase-dependent fashion. Finally, the carboxyl-terminal domain of RNA POL II fused to glutathione S-transferase is phosphorylated in reaction mixtures containing complexes pulled down with ICP22 or cdk9 immune precipitated from lysates of wild-type parent virus or ΔUL13 but not ΔUS3 mutant-infected cells. The experiments described here place ICP22 and cdk9 in a complex with the carboxyl-terminal domain of RNA POL II. At the same time we confirm the requirement of ICP22 and the UL13 protein kinase in the posttranslational modification of RNA POL II that alters its electrophoretic mobility, although US3 kinase appears to play a role in a cell-type-dependent fashion.

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