English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/188787
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


HIF1α suppresses tumor cell proliferation through inhibition of aspartate biosynthesis

AuthorsMeléndez-Rodríguez, Florinda; Urrutia, Andrés A.; Lorendeau, Doriane; Rinaldi, Gianmarco; Roche, Olga; Böğürcü-Seidel, Nuray; Ortega-Muelas, Marta; Mesa-Ciller, Claudia; Turiel, Guillermo; Bouthelier, Antonio; Hernansanz-Agustín, Pablo; Elorza, Ainara; Escasany, Elia; Yang Li, Qilong Oscar; Torres-Capelli, Mar; Tello, Daniel; Fuertes, Esther; Fraga, Enrique; Martínez-Ruiz, Antonio ; Pérez, Belén ; Giménez-Bachs, Jose Miguel; Salinas-Sánchez, Antonio S.; Acker, Till; Sánchez-Prieto, Ricardo; Fendt, Sarah-Maria; De Bock, Katrien; Aragonés, Julián
Aspartate biosynthesis
Renal cell carcinoma
Issue Date2019
CitationCell Reports 26(9): 2257-2265.e4
AbstractCellular aspartate drives cancer cell proliferation, but signaling pathways that rewire aspartate biosynthesis to control cell growth remain largely unknown. Hypoxia-inducible factor-1α (HIF1α) can suppress tumor cell proliferation. Here, we discovered that HIF1α acts as a direct repressor of aspartate biosynthesis involving the suppression of several key aspartate-producing proteins, including cytosolic glutamic-oxaloacetic transaminase-1 (GOT1) and mitochondrial GOT2. Accordingly, HIF1α suppresses aspartate production from both glutamine oxidation as well as the glutamine reductive pathway. Strikingly, the addition of aspartate to the culture medium is sufficient to relieve HIF1α-dependent repression of tumor cell proliferation. Furthermore, these key aspartate-producing players are specifically repressed in VHL-deficient human renal carcinomas, a paradigmatic tumor type in which HIF1α acts as a tumor suppressor, highlighting the in vivo relevance of these findings. In conclusion, we show that HIF1α inhibits cytosolic and mitochondrial aspartate biosynthesis and that this mechanism is the molecular basis for HIF1α tumor suppressor activity.
Publisher version (URL)https://doi.org/10.1016/j.celrep.2019.01.106
Appears in Collections:(IIBM) Artículos
(CBM) Artículos
Files in This Item:
File Description SizeFormat 
hifbio.pdf2,18 MBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.