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Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7876-81. doi: 10.1073/pnas.1600587113. Epub 2016 Jun 24.

A viral kinase mimics S6 kinase to enhance cell proliferation.

Author information

1
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
2
Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
3
Pepscan Presto BV, 8243 Lelystad, The Netherlands;
4
Department of Dermatology, University of California Davis School of Medicine, Sacramento, CA 95817; Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817;
5
Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817; University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817;
6
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; R. L. Juliano Structural Bioinformatics Core Facility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Center for Structural Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
7
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; damania@med.unc.edu.

Abstract

Viruses depend upon the host cell for manufacturing components of progeny virions. To mitigate the inextricable dependence on host cell protein synthesis, viruses can modulate protein synthesis through a variety of mechanisms. We report that the viral protein kinase (vPK) encoded by open reading frame 36 (ORF36) of Kaposi's sarcoma-associated herpesvirus (KSHV) enhances protein synthesis by mimicking the function of the cellular protein S6 kinase (S6KB1). Similar to S6KB1, vPK phosphorylates the ribosomal S6 protein and up-regulates global protein synthesis. vPK also augments cellular proliferation and anchorage-independent growth. Furthermore, we report that both vPK and S6KB1 phosphorylate the enzyme 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) and that both kinases promote endothelial capillary tubule formation.

KEYWORDS:

KSHV; ORF36; S6K; cell signaling; viral protein kinase

PMID:
27342859
PMCID:
PMC4948314
DOI:
10.1073/pnas.1600587113
[Indexed for MEDLINE]
Free PMC Article

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