The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4
| العنوان: | The tumour suppressor PTEN mediates a negative regulation of the E3 ubiquitin-protein ligase Nedd4 |
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| المؤلفون: | Cheolju Lee, Seung-Rock Lee, Ki-Sun Kwon, Chae Young Hwang, Younghee Ahn |
| المصدر: | Biochemical Journal. 412:331-338 |
| بيانات النشر: | Portland Press Ltd., 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Proteome, Transcription, Genetic, Nedd4 Ubiquitin Protein Ligases, Ubiquitin-Protein Ligases, Apoptosis, X-Linked Inhibitor of Apoptosis Protein, NEDD4, macromolecular substances, Biochemistry, Mice, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Animals, Humans, Tensin, PTEN, LY294002, RNA, Small Interfering, Molecular Biology, PI3K/AKT/mTOR pathway, Regulation of gene expression, chemistry.chemical_classification, DNA ligase, Endosomal Sorting Complexes Required for Transport, biology, E3 Ubiquitin-Protein Ligase NEDD4, Tumor Suppressor Proteins, PTEN Phosphohydrolase, Cell Biology, Molecular biology, Gene Expression Regulation, chemistry, Caspases, NIH 3T3 Cells, biology.protein, Proto-Oncogene Proteins c-akt, HeLa Cells, Signal Transduction |
| الوصف: | 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. |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c27cdc2ef2842b106d6871ee512a7974Test https://doi.org/10.1042/bj20071403Test |
| رقم الانضمام: | edsair.doi.dedup.....c27cdc2ef2842b106d6871ee512a7974 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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