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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-7-28
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pubmed:abstractText |
The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517. Consequently, PML mutants that are resistant to CK2 phosphorylation display increased tumor-suppressive functions. In a faithful mouse model of lung cancer, we demonstrate that Pml inactivation leads to increased tumorigenesis. Furthermore, CK2 pharmacological inhibition enhances the PML tumor-suppressive property in vivo. Importantly, we found an inverse correlation between CK2 kinase activity and PML protein levels in human lung cancer-derived cell lines and primary specimens. These data identify a key posttranslational mechanism that controls PML protein levels and provide therapeutic means toward PML restoration through CK2 inhibition.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/4,5,6,7-tetrabromobenzotriazole,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hemagglutinins,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PML protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pml protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sorbitol,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Triazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
269-83
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16873060-Amino Acid Sequence,
pubmed-meshheading:16873060-Amino Acid Substitution,
pubmed-meshheading:16873060-Animals,
pubmed-meshheading:16873060-Apoptosis,
pubmed-meshheading:16873060-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:16873060-Casein Kinase II,
pubmed-meshheading:16873060-Cell Line,
pubmed-meshheading:16873060-Cell Line, Transformed,
pubmed-meshheading:16873060-Cell Line, Tumor,
pubmed-meshheading:16873060-Enzyme Activation,
pubmed-meshheading:16873060-Enzyme Inhibitors,
pubmed-meshheading:16873060-Genes, Tumor Suppressor,
pubmed-meshheading:16873060-Green Fluorescent Proteins,
pubmed-meshheading:16873060-Hemagglutinins,
pubmed-meshheading:16873060-Humans,
pubmed-meshheading:16873060-Leupeptins,
pubmed-meshheading:16873060-Lung Neoplasms,
pubmed-meshheading:16873060-Mice,
pubmed-meshheading:16873060-Mice, Transgenic,
pubmed-meshheading:16873060-Molecular Sequence Data,
pubmed-meshheading:16873060-NIH 3T3 Cells,
pubmed-meshheading:16873060-Neoplasm Proteins,
pubmed-meshheading:16873060-Nuclear Proteins,
pubmed-meshheading:16873060-Phosphorylation,
pubmed-meshheading:16873060-Proteasome Endopeptidase Complex,
pubmed-meshheading:16873060-Protein Structure, Tertiary,
pubmed-meshheading:16873060-Protein Subunits,
pubmed-meshheading:16873060-RNA, Small Interfering,
pubmed-meshheading:16873060-Sequence Deletion,
pubmed-meshheading:16873060-Serine,
pubmed-meshheading:16873060-Sorbitol,
pubmed-meshheading:16873060-Transcription Factors,
pubmed-meshheading:16873060-Transcriptional Activation,
pubmed-meshheading:16873060-Triazoles,
pubmed-meshheading:16873060-Tumor Suppressor Proteins,
pubmed-meshheading:16873060-Ubiquitin,
pubmed-meshheading:16873060-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2006
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pubmed:articleTitle |
A CK2-dependent mechanism for degradation of the PML tumor suppressor.
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pubmed:affiliation |
Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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