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000290199 1001_ $$aLevy, Tal$$b0
000290199 245__ $$amTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.
000290199 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000290199 520__ $$aEnergetic stress compels cells to evolve adaptive mechanisms to adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls cell viability during glucose starvation is not well understood. Here we show that the mTORC1 effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection to mammalian cells and budding yeast under glucose starvation. Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty acid synthesis via translational repression of Acetyl-CoA Carboxylase 1 (ACC1), thereby mitigating oxidative stress. This has important relevance for cancer, as oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACC1 expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 expression is associated with poor outcomes in several cancer types. Our data reveal that the mTORC1-4EBP1/2 axis provokes a metabolic switch essential for survival during glucose starvation which is exploited by transformed and tumor cells.
000290199 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000290199 650_2 $$2MeSH$$aMechanistic Target of Rapamycin Complex 1: metabolism
000290199 650_2 $$2MeSH$$aMechanistic Target of Rapamycin Complex 1: genetics
000290199 650_2 $$2MeSH$$aGlucose: metabolism
000290199 650_2 $$2MeSH$$aAcetyl-CoA Carboxylase: metabolism
000290199 650_2 $$2MeSH$$aAcetyl-CoA Carboxylase: genetics
000290199 650_2 $$2MeSH$$aHumans
000290199 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: metabolism
000290199 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: genetics
000290199 650_2 $$2MeSH$$aFatty Acids: metabolism
000290199 650_2 $$2MeSH$$aAnimals
000290199 650_2 $$2MeSH$$aCell Survival
000290199 650_2 $$2MeSH$$aCell Cycle Proteins: metabolism
000290199 650_2 $$2MeSH$$aCell Cycle Proteins: genetics
000290199 650_2 $$2MeSH$$aMice
000290199 650_2 $$2MeSH$$aNADP: metabolism
000290199 650_2 $$2MeSH$$aProtein Biosynthesis
000290199 650_2 $$2MeSH$$aPhosphoproteins: metabolism
000290199 650_2 $$2MeSH$$aPhosphoproteins: genetics
000290199 650_2 $$2MeSH$$aOxidative Stress
000290199 650_2 $$2MeSH$$aCell Line, Tumor
000290199 650_2 $$2MeSH$$aEukaryotic Initiation Factors: metabolism
000290199 650_2 $$2MeSH$$aEukaryotic Initiation Factors: genetics
000290199 7001_ $$aVoeltzke, Kai$$b1
000290199 7001_ $$aHruby, Laura$$b2
000290199 7001_ $$00000-0002-9876-0141$$aAlasad, Khawla$$b3
000290199 7001_ $$aBas, Zuelal$$b4
000290199 7001_ $$0P:(DE-He78)7b7131e0870c28d432e48873d295460f$$aSnaebjörnsson, Marteinn Thor$$b5$$udkfz
000290199 7001_ $$aMarciano, Ran$$b6
000290199 7001_ $$aScharov, Katerina$$b7
000290199 7001_ $$00000-0001-7052-7084$$aPlanque, Mélanie$$b8
000290199 7001_ $$aVriens, Kim$$b9
000290199 7001_ $$aChristen, Stefan$$b10
000290199 7001_ $$0P:(DE-He78)0921630050b802a96db645029b1a982b$$aFunk, Cornelius$$b11$$udkfz
000290199 7001_ $$aHassiepen, Christina$$b12
000290199 7001_ $$00000-0001-8841-0490$$aKahler, Alisa$$b13
000290199 7001_ $$aHeider, Beate$$b14
000290199 7001_ $$0P:(DE-He78)2d0b899984e41ffa8cb15d799d32afd1$$aPicard, Daniel Joseph$$b15$$udkfz
000290199 7001_ $$00000-0002-1798-8954$$aLim, Jonathan K M$$b16
000290199 7001_ $$aStefanski, Anja$$b17
000290199 7001_ $$aBendrin, Katja$$b18
000290199 7001_ $$00000-0002-0070-8143$$aVargas-Toscano, Andres$$b19
000290199 7001_ $$00000-0002-6021-1841$$aKahlert, Ulf D$$b20
000290199 7001_ $$aStühler, Kai$$b21
000290199 7001_ $$0P:(DE-He78)a244aa021112b9002419791434bbc71c$$aRemke, Marc$$b22
000290199 7001_ $$aElkabets, Moshe$$b23
000290199 7001_ $$0P:(DE-He78)7a590ab95c6f7ba52880452da78ecd6c$$aGrünewald, Thomas$$b24$$udkfz
000290199 7001_ $$00000-0001-9340-3113$$aReichert, Andreas S$$b25
000290199 7001_ $$00000-0001-6018-9296$$aFendt, Sarah-Maria$$b26
000290199 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b27$$udkfz
000290199 7001_ $$0P:(DE-HGF)0$$aReifenberger, Guido$$b28
000290199 7001_ $$00000-0003-2985-7115$$aRotblat, Barak$$b29
000290199 7001_ $$00000-0002-2299-8989$$aLeprivier, Gabriel$$b30
000290199 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-48386-y$$gVol. 15, no. 1, p. 4083$$n1$$p4083$$tNature Communications$$v15$$x2041-1723$$y2024
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