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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2000-9-5
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pubmed:abstractText |
p12(DOC-1) is a growth suppressor identified and isolated from normal keratinocytes. Ectopic expression of p12(DOC-1) in squamous carcinoma cells led to the reversion of in vitro transformation phenotypes including anchorage independence, doubling time, and morphology. Here we report that p12(DOC-1) associates with DNA polymerase alpha/primase (pol-alpha:primase) in vitro and in cells. The pol-alpha:primase binding domain in p12(DOC-1) is mapped to the amino-terminal six amino acid (MSYKPN). The biological effect of p12(DOC-1) on pol-alpha:primase was examined using in vitro DNA replication assays. Using the SV40 DNA replication assay, p12(DOC-1) suppresses DNA replication, leveling at approximately 50%. Similar results were obtained using the M13 single-stranded DNA synthesis assay. Analysis of the DNA replication products revealed that p12(DOC-1) affects the initiation step, not the elongation phase. The p12(DOC-1) suppression of DNA replication is likely to be mediated either by a direct inhibitory effect on pol-alpha:primase or by its effect on cyclin-dependent kinase 2 (CDK2), a recently identified p12(DOC-1)-associated protein known to stimulate DNA replication by phosphorylating pol-alpha:primase. p12(DOC-1) suppresses CDK2-mediated phosphorylation of pol-alpha:primase. These data support a role of p12(DOC-1) as a regulator of DNA replication by direct inhibition of pol-alpha:primase or by negatively regulating the CDK2-mediated phosphorylation of pol-alpha:primase.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2AP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Polymerase I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA polymerase alpha-primase,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0892-6638
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1318-24
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10877824-Amino Acid Sequence,
pubmed-meshheading:10877824-Animals,
pubmed-meshheading:10877824-Binding Sites,
pubmed-meshheading:10877824-CDC2-CDC28 Kinases,
pubmed-meshheading:10877824-Cell Line,
pubmed-meshheading:10877824-Cyclin-Dependent Kinase 2,
pubmed-meshheading:10877824-Cyclin-Dependent Kinases,
pubmed-meshheading:10877824-DNA Polymerase I,
pubmed-meshheading:10877824-DNA Primase,
pubmed-meshheading:10877824-DNA Replication,
pubmed-meshheading:10877824-Enzyme Inhibitors,
pubmed-meshheading:10877824-Growth Inhibitors,
pubmed-meshheading:10877824-Humans,
pubmed-meshheading:10877824-Phosphorylation,
pubmed-meshheading:10877824-Protein Structure, Tertiary,
pubmed-meshheading:10877824-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10877824-Proteins,
pubmed-meshheading:10877824-Recombinant Fusion Proteins,
pubmed-meshheading:10877824-Tumor Suppressor Proteins
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pubmed:year |
2000
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pubmed:articleTitle |
p12(DOC-1), a growth suppressor, associates with DNA polymerase alpha/primase.
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pubmed:affiliation |
Laboratory of Molecular Pathology, Division of Oral Pathology, and. Harvard University, School of Dental Medicine, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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