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PMID: 9151805 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1.

Journal of virology ·Vol. 71 ·No. 6 ·1997-06-00 ·Pages 4193-8

Godden-Kent D, Talbot SJ, Boshoff C, Chang Y, Moore P, Weiss RA, Mittnacht S

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is a novel gammaherpesvirus implicated in the cause of Kaposi's sarcoma and certain malignancies of lymphatic origin. One of the candidate genes possibly involved in promoting tumor development is an open reading frame (ORF) with sequence similarity to human type D cyclin genes. This cyclin-like gene, when expressed in tissue culture cells, promotes phosphorylation and inactivation of the retinoblastoma tumor suppressor protein and thereby may result in deregulation of cell division control. We report here the biochemical characterization of this cyclin (KSHV-cyc) and the kinase activity that it elicits upon expression in tissue culture cells. We demonstrate that the kinase activity associated with KSHV-cyc is sensitive to the cdk inhibitor p27 (KIP) and due to activation of cdk6. However, in contrast to cdk6 activated by cellular type D cyclins, the cdk6 activated by KSHV-cyc is capable of phosphorylating not only the retinoblastoma protein but also histone H1. This finding implies that activation by KSHV-cyc alters the substrate preference of this cdk. This may have important physiological consequences in that the kinase activity triggered by this viral cyclin may abrogate cell cycle checkpoints in addition to those targeted by cellular cyclin D-cdk6 kinase.

MeSH Terms
Animals COS Cells Cell Cycle Proteins Cells, Cultured Chlorocebus aethiops Cyclin-Dependent Kinase 6 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases Cyclins/physiology Dogs Enzyme Activation Herpesvirus 8, Human/genetics Histones/metabolism Microtubule-Associated Proteins/pharmacology Phosphorylation Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Retinoblastoma Protein/metabolism Spodoptera Tumor Suppressor Proteins
Chemicals
Cell Cycle Proteins Cyclins Histones Microtubule-Associated Proteins Retinoblastoma Protein Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Protein Serine-Threonine Kinases Cyclin-Dependent Kinase 6 Cyclin-Dependent Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Godden-Kent D
Centre for Molecular and Cell Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Talbot S J
Boshoff C
Chang Y
Moore P
Weiss R A
Mittnacht S
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.6.4193-4198.1997
Published
1997-06-00
Pages
4193-8
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191633
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.71.6.4193-4198.1997 PMC Full Text View journal details
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