The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO
| العنوان: | The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO |
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| المؤلفون: | Anna Pilsl, Jörg Tatzelt, Daniel Krappmann, Silvana Hrelia, Wolfgang Wurst, Maria Patra, Anne Kathrin Müller-Rischart, Carolin Schweimer, Thomas Langer, Dietrich Trümbach, Gunnar Dittmar, Maria Funke, Alexandra Deinlein, Regina Peis, Patrick Beaudette, Elisa Motori, Konstanze F. Winklhofer, Peer-Hendrik Kuhn, Kamyar Hadian, Stefan F. Lichtenthaler |
| المساهمون: | Müller-Rischart A.K., Pilsl A., Beaudette P., Patra M., Hadian K., Funke M., Peis R., Deinlein A., Schweimer C., Kuhn P.H., Lichtenthaler S.F., Motori E., Hrelia S., Wurst W., Trümbach D., Langer T., Krappmann D., Dittmar G., Tatzelt J., Winklhofer K.F. |
| المصدر: | Mol Cell Molecular cell 49(5), 908-921 (2013). doi:10.1016/j.molcel.2013.01.036 Mol. Cell 49, 908-921 (2013) |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | UBIQUINATION, parkin protein, Apoptosis, Mitochondrion, PARKIN, Parkin, Mice, Ubiquitin, MITOCHONDRIA, genetics [Parkinson Disease], Mitophagy, genetics [Ubiquitination], Neurons, Mice, Knockout, genetics [Ubiquitin-Protein Ligases], biology, Intracellular Signaling Peptides and Proteins, NF-kappa B, Parkinson Disease, Cell biology, Ubiquitin ligase, metabolism [Neurons], metabolism [NF-kappa B], Signal transduction, metabolism [Intracellular Signaling Peptides and Proteins], metabolism [Fibroblasts], Signal Transduction, Ubiquitin-Protein Ligases, metabolism [Parkinson Disease], NF-kB ESSENTIAL MODULATOR, Transfection, PARKINSON’S DISEASE, metabolism [Ubiquitin-Protein Ligases], Downregulation and upregulation, NEMO protein, mouse, Animals, Humans, ddc:610, Molecular Biology, HEK 293 cells, Ubiquitination, Cell Biology, Fibroblasts, metabolism [Mitochondria], Molecular biology, nervous system diseases, HEK293 Cells, biology.protein, genetics [Intracellular Signaling Peptides and Proteins], genetics [NF-kappa B] |
| الوصف: | Parkin, a RING-between-RING-type E3 ubiquitin ligase associated with Parkinson's disease, has a wide neuroprotective activity, preventing cell death in various stress paradigms. We identified a stress-protective pathway regulated by parkin that links NF-kappa B signaling and mitochondrial integrity via linear ubiquitination. Under cellular stress, parkin is recruited to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-kappa B essential modulator (NEMO), which is essential for canonical NF-kappa B signaling. As a result, the mitochondrial guanosine triphosphatase OPA1 is transcriptionally upregulated via NF-kappa B-responsive promoter elements for maintenance of mitochondrial integrity and protection from stress-induced cell death. Parkin-induced stress protection is lost in the absence of either NEMO or OPA1, but not in cells defective for the mitophagy pathway. Notably, in parkin-deficient cells linear ubiquitination of NEMO, activation of NF-kappa B, and upregulation of OPA1 are significantly reduced in response to TNF-alpha stimulation, supporting the physiological relevance of parkin in regulating this antiapoptotic pathway. |
| وصف الملف: | STAMPA; application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f741d75d3bc8ba3566b658fa6f4fc23eTest https://hdl.handle.net/21.11116/0000-000B-7ABD-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f741d75d3bc8ba3566b658fa6f4fc23e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |