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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2005-6-6
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pubmed:abstractText |
The tumor suppressor function of the von Hippel-Lindau protein (pVHL) has previously been linked to its role in regulating hypoxia-inducible factor levels. However, VHL gene mutations suggest a hypoxia-inducible factor-independent function for the N-terminal acidic domain in tumor suppression. Here, we report that phosphorylation of the N-terminal acidic domain of pVHL by casein kinase-2 is essential for its tumor suppressor function. This post-translational modification did not affect the levels of hypoxia-inducible factor; however, it did change the binding of pVHL to another known binding partner, fibronectin. Cells expressing phospho-defective mutants caused improper fibronectin matrix deposition and demonstrated retarded tumor formation in mice. We propose that phosphorylation of the acidic domain plays a role in the regulation of proper fibronectin matrix deposition and that this may be relevant for the development of VHL-associated malignancies.
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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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hif1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/VHL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22205-11
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15824109-Animals,
pubmed-meshheading:15824109-Anoxia,
pubmed-meshheading:15824109-Cell Line,
pubmed-meshheading:15824109-Chromatography, Gel,
pubmed-meshheading:15824109-DNA-Binding Proteins,
pubmed-meshheading:15824109-Dose-Response Relationship, Drug,
pubmed-meshheading:15824109-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15824109-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15824109-Fibronectins,
pubmed-meshheading:15824109-Humans,
pubmed-meshheading:15824109-Hypoxia-Inducible Factor 1,
pubmed-meshheading:15824109-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15824109-Immunoblotting,
pubmed-meshheading:15824109-Immunoprecipitation,
pubmed-meshheading:15824109-Mice,
pubmed-meshheading:15824109-Mice, SCID,
pubmed-meshheading:15824109-Mutation,
pubmed-meshheading:15824109-Neoplasm Transplantation,
pubmed-meshheading:15824109-Nuclear Proteins,
pubmed-meshheading:15824109-Phosphorylation,
pubmed-meshheading:15824109-Plasmids,
pubmed-meshheading:15824109-Protein Binding,
pubmed-meshheading:15824109-Protein Processing, Post-Translational,
pubmed-meshheading:15824109-Protein Structure, Tertiary,
pubmed-meshheading:15824109-Time Factors,
pubmed-meshheading:15824109-Transcription Factors,
pubmed-meshheading:15824109-Transfection,
pubmed-meshheading:15824109-Tumor Suppressor Proteins,
pubmed-meshheading:15824109-Ubiquitin,
pubmed-meshheading:15824109-Ubiquitin-Protein Ligases,
pubmed-meshheading:15824109-Von Hippel-Lindau Tumor Suppressor Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Tumor suppression by the von Hippel-Lindau protein requires phosphorylation of the acidic domain.
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pubmed:affiliation |
Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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