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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 |
2008-5-9
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pubmed:abstractText |
The tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10; a phosphatidylinositol 3-phosphatase) is a multifunctional protein deregulated in many types of cancer. It is suggested that a number of proteins that relate with PTEN functionally or physically have not yet been found. In order to search for PTEN-interacting proteins that might be crucial in the regulation of PTEN, we exploited a proteomics-based approach. PTEN-expressing NIH 3T3 cell lysates were used in affinity chromatography and then analysed by LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem MS). A total of 93 proteins were identified. Among the proteins identified, we concentrated on the E3 ubiquitin-protein ligase Nedd4 (neural-precursor-cell-expressed, developmentally down-regulated gene 4), and performed subsequent validation experiments using HeLa cells. Nedd4 inhibited PTEN-induced apoptotic cell death and, conversely, the Nedd4 level was down-regulated by PTEN. The down-regulation effect was diminished by a mutation (C124S) in the catalytic site of PTEN. Nedd4 expression was also decreased by a PI3K (phosphoinositide 3-kinase) inhibitor, LY294002, suggesting that the regulation is dependent on the phosphatase-kinase activity of the PTEN-PI3K/Akt pathway. Semi-quantitative real-time PCR analysis revealed that Nedd4 was transcriptionally regulated by PTEN. Thus our results have important implications regarding the roles of PTEN upon the E3 ubquitin ligase Nedd4 as a negative feedback regulator as well as a substrate.
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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/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Endosomal Sorting Complexes...,
http://linkedlifedata.com/resource/pubmed/chemical/Nedd4 ubiquitin protein ligases,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteome,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
412
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
331-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18307411-Animals,
pubmed-meshheading:18307411-Apoptosis,
pubmed-meshheading:18307411-Caspases,
pubmed-meshheading:18307411-Endosomal Sorting Complexes Required for Transport,
pubmed-meshheading:18307411-Gene Expression Regulation,
pubmed-meshheading:18307411-HeLa Cells,
pubmed-meshheading:18307411-Humans,
pubmed-meshheading:18307411-Mice,
pubmed-meshheading:18307411-NIH 3T3 Cells,
pubmed-meshheading:18307411-PTEN Phosphohydrolase,
pubmed-meshheading:18307411-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18307411-Proteome,
pubmed-meshheading:18307411-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18307411-RNA, Small Interfering,
pubmed-meshheading:18307411-Signal Transduction,
pubmed-meshheading:18307411-Transcription, Genetic,
pubmed-meshheading:18307411-Tumor Suppressor Proteins,
pubmed-meshheading:18307411-Ubiquitin-Protein Ligases,
pubmed-meshheading:18307411-X-Linked Inhibitor of Apoptosis Protein
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pubmed:year |
2008
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pubmed:articleTitle |
The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4.
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pubmed:affiliation |
Life Sciences Division, Korea Institute of Science and Technology, Seoul 136-791, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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