Subcellular Localization and Mitotic Interactome Analyses Identify SIRT4 as a Centrosomally Localized and Microtubule Associated Protein
| العنوان: | Subcellular Localization and Mitotic Interactome Analyses Identify SIRT4 as a Centrosomally Localized and Microtubule Associated Protein |
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| المؤلفون: | Mohammad Reza Ahmadian, Helmut Hanenberg, Nina Overbeck, Andreas Kefalas, Alexander Lang, Patrick Verhülsdonk, Anja Stefanski, Jürgen Scheller, Kai Stühler, Andreas S. Reichert, Constanze Wiek, Simone Altinoluk-Hambüchen, Christoph Bross, Christian Mielke, Laura Bergmann, Iris Fey, Reiner U. Jänicke, Dennis Sohn, Roland P. Piekorz |
| المصدر: | Cells, Vol 9, Iss 1950, p 1950 (2020) Cells Volume 9 Issue 9 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | mitosis, SIRT3, Chemistry, Microtubule-associated protein, Medizin, interactome, General Medicine, HDAC6, Mitochondrion, Cell cycle, Article, Cell biology, Mitochondrial Proteins, sirtuin, SIRT4, centrosome, lcsh:Biology (General), Microtubule, Centrosome, Acetylation, Humans, Sirtuins, Microtubule-Associated Proteins, lcsh:QH301-705.5, Mitosis |
| الوصف: | The stress-inducible and senescence-associated tumor suppressor SIRT4, a member of the family of mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5), regulates bioenergetics and metabolism via NAD+-dependent enzymatic activities. Next to the known mitochondrial location, we found that a fraction of endogenous or ectopically expressed SIRT4, but not SIRT3, is present in the cytosol and predominantly localizes to centrosomes. Confocal spinning disk microscopy revealed that SIRT4 is found during the cell cycle dynamically at centrosomes with an intensity peak in G2 and early mitosis. Moreover, SIRT4 precipitates with microtubules and interacts with structural (&alpha &beta tubulin, &gamma tubulin, TUBGCP2, TUBGCP3) and regulatory (HDAC6) microtubule components as detected by co-immunoprecipitation and mass spectrometric analyses of the mitotic SIRT4 interactome. Overexpression of SIRT4 resulted in a pronounced decrease of acetylated &alpha tubulin (K40) associated with altered microtubule dynamics in mitotic cells. SIRT4 or the N-terminally truncated variant SIRT4(&Delta N28), which is unable to translocate into mitochondria, delayed mitotic progression and reduced cell proliferation. This study extends the functional roles of SIRT4 beyond mitochondrial metabolism and provides the first evidence that SIRT4 acts as a novel centrosomal/microtubule-associated protein in the regulation of cell cycle progression. Thus, stress-induced SIRT4 may exert its role as tumor suppressor through mitochondrial as well as extramitochondrial functions, the latter associated with its localization at the mitotic spindle apparatus. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a7918a082681010a9257a4e45e90c12Test https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85089977965Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a7918a082681010a9257a4e45e90c12 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |