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PMID: 8380893 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Control of simian virus 40 DNA replication by the HeLa cell nuclear kinase casein kinase I.

Molecular and cellular biology ·Vol. 13 ·No. 2 ·1993-02-00 ·Pages 1202-11

Cegielska A, Virshup DM

Abstract

The initiation of simian virus 40 (SV40) DNA replication is regulated by the phosphorylation state of the viral initiator protein, large T antigen. We describe the purification from HeLa cell nuclei of a 35-kDa serine/threonine protein kinase that phosphorylates T antigen at sites that are phosphorylated in vivo and thereby inhibits its ability to initiate SV40 DNA replication. The inhibition of both origin unwinding and DNA replication by the kinase is reversed by protein phosphatase 2A. As determined by molecular weight, substrate specificity, autophosphorylation, immunoreactivity, and limited sequence analysis, this kinase appears to be identical to casein kinase I, a ubiquitous serine/threonine protein kinase that is closely related to a yeast kinase involved in DNA metabolism. The HeLa cell phosphorylation cycle that controls the initiation of SV40 DNA replication may also play a role in cellular DNA metabolism.

MeSH Terms
Adenosine Triphosphate/metabolism Amino Acid Sequence Casein Kinases Cell Nucleus/enzymology,microbiology DNA Replication DNA, Viral/biosynthesis Electrophoresis, Polyacrylamide Gel Enzyme Activation HeLa Cells Humans Molecular Sequence Data Phosphoprotein Phosphatases/metabolism Phosphorylation Protein Kinase Inhibitors Protein Kinases/metabolism Protein Phosphatase 2 Simian virus 40/genetics Temperature
Chemicals
DNA, Viral Protein Kinase Inhibitors Adenosine Triphosphate Protein Kinases Casein Kinases Phosphoprotein Phosphatases Protein Phosphatase 2
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cegielska A
Department of Cellular, Viral and Molecular Biology, University of Utah, Salt Lake City 84112.
Virshup D M
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46 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.2.1202-1211.1993
Published
1993-02-00
Pages
1202-11
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359005
Subset
IM
Grants
NIAID NIH HHS · AI 31657 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.2.1202-1211.1993 PMC Full Text View journal details
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