Academic Journal
c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder
| العنوان: | c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder |
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| المؤلفون: | Pablo S. Contreras, Pablo J. Tapia, Lila González-Hódar, Ivana Peluso, Chiara Soldati, Gennaro Napolitano, Maria Matarese, Macarena Las Heras, Cristian Valls, Alexis Martinez, Elisa Balboa, Juan Castro, Nancy Leal, Frances M. Platt, Andrzej Sobota, Dominic Winter, Andrés D. Klein, Diego L. Medina, Andrea Ballabio, Alejandra R. Alvarez, Silvana Zanlungo |
| المصدر: | iScience, Vol 23, Iss 11, Pp 101691- (2020) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2020 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Biological Sciences, Molecular Biology, Cell Biology, Science |
| الوصف: | Summary: The transcription factor EB (TFEB) has emerged as a master regulator of lysosomal biogenesis, exocytosis, and autophagy, promoting the clearance of substrates stored in cells. c-Abl is a tyrosine kinase that participates in cellular signaling in physiological and pathophysiological conditions. In this study, we explored the connection between c-Abl and TFEB. Here, we show that under pharmacological and genetic c-Abl inhibition, TFEB translocates into the nucleus promoting the expression of its target genes independently of its well-known regulator, mammalian target of rapamycin complex 1. Active c-Abl induces TFEB phosphorylation on tyrosine and the inhibition of this kinase promotes lysosomal biogenesis, autophagy, and exocytosis. c-Abl inhibition in Niemann-Pick type C (NPC) models, a neurodegenerative disease characterized by cholesterol accumulation in lysosomes, promotes a cholesterol-lowering effect in a TFEB-dependent manner. Thus, c-Abl is a TFEB regulator that mediates its tyrosine phosphorylation, and the inhibition of c-Abl activates TFEB promoting cholesterol clearance in NPC models. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2589-0042 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S258900422030883X; https://doaj.org/toc/2589-0042; https://doaj.org/article/c6a46857605147c4a1da866ca411c8d6 |
| DOI: | 10.1016/j.isci.2020.101691 |
| الاتاحة: | https://doi.org/10.1016/j.isci.2020.101691 https://doaj.org/article/c6a46857605147c4a1da866ca411c8d6 |
| رقم الانضمام: | edsbas.ED72AAFD |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25890042 |
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| DOI: | 10.1016/j.isci.2020.101691 |