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Título: | Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism | Autor: | Bertolio, Rebecca Napoletano, Francesco Mano, Miguel Maurer-Stroh, Sebastian Fantuz, Marco Zannini, Alessandro Bicciato, Silvio Sorrentino, Giovanni Del Sal, Giannino |
Data: | 22-Mar-2019 | Editora: | Springer Nature | Projeto: | We acknowledge support by the Italian Health Ministry (RF-2011-02346976 to G.D.S.), the Italian University and Research Ministry (PRIN- 2015-8KZKE3), the Cariplo Foundation (grant no. 2014-0812), Beneficentia-Stiftung, the European Regional Development Fund Interreg Italia-Österreich (PreCanMed ITAT1009), Fondazione CRTrieste and Regione Autonoma Friuli Venezia Giulia (Contributo ex art. 15 L.R. 17/2014) to G.D.S. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and AIRC Special Program Molecular Clinical Oncology ‘5 per mille’ (grant no. 10016) to G.D.S. and S.B., and AIRC IG (grant no. 17659) to G.D.S. M.M. was supported by the FCT Investigator Programme IF/00694/2013 from the Portuguese Foundation for Science and Technology (FCT), Portugal. G.S. is a recipient of a FEBS long-term fellowship. R.B. and M.F. are supported by a FIRC-AIRC fellowship for Italy. F.N. was supported by a European Union FP7/ Associazione Italiana per la Ricerca sul Cancro (AIRC) Reintegration Grant (iCARE N° 17885) and a University of Trieste FRA 2018 Starting Grant. We thank the Confocal microscopy facility of the University of Trieste. We also thank F. Feiguin (International Centre for Genetic Engineering and Biotechnology, Trieste, Italy) for providing Drosophila cells and lines, and the Vienna Drosophila Resource Center, the Bloomington Drosophila Stock Center, P. Bellosta (University of Trento, Italy), and B. Mollereau (Ecole Normale Superierure de Lyon, France) for providing Drosophila lines. | Título da revista, periódico, livro ou evento: | Nature Communications | Volume: | 10 | Número: | 1 | Resumo: | Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In vertebrates, SREBP activation is mainly controlled by a complex and well-characterized feedback mechanism mediated by cholesterol, a crucial bio-product of the SREBP-activated mevalonate pathway. In this work, we identified acto-myosin contractility and mechanical forces imposed by the extracellular matrix (ECM) as SREBP1 regulators. SREBP1 control by mechanical cues depends on geranylgeranyl pyrophosphate, another key bio-product of the mevalonate pathway, and impacts on stem cell fate in mouse and on fat storage in Drosophila. Mechanistically, we show that activation of AMP-activated protein kinase (AMPK) by ECM stiffening and geranylgeranylated RhoA-dependent acto-myosin contraction inhibits SREBP1 activation. Our results unveil an unpredicted and evolutionary conserved role of SREBP1 in rewiring cell metabolism in response to mechanical cues. | URI: | https://hdl.handle.net/10316/107184 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-019-09152-7 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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Sterol-regulatory-element-binding-protein-1-couples-mechanical-cues-and-lipid-metabolismNature-Communications.pdf | 2.44 MB | Adobe PDF | Ver/Abrir |
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