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@ARTICLE{Levy:290199,
author = {T. Levy and K. Voeltzke and L. Hruby and K. Alasad and Z.
Bas and M. T. Snaebjörnsson$^*$ and R. Marciano and K.
Scharov and M. Planque and K. Vriens and S. Christen and C.
Funk$^*$ and C. Hassiepen and A. Kahler and B. Heider and D.
J. Picard$^*$ and J. K. M. Lim and A. Stefanski and K.
Bendrin and A. Vargas-Toscano and U. D. Kahlert and K.
Stühler and M. Remke$^*$ and M. Elkabets and T.
Grünewald$^*$ and A. S. Reichert and S.-M. Fendt and A.
Schulze$^*$ and G. Reifenberger$^*$ and B. Rotblat and G.
Leprivier},
title = {m{TORC}1 regulates cell survival under glucose starvation
through 4{EBP}1/2-mediated translational reprogramming of
fatty acid metabolism.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-01032},
pages = {4083},
year = {2024},
abstract = {Energetic 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.},
keywords = {Mechanistic Target of Rapamycin Complex 1: metabolism /
Mechanistic Target of Rapamycin Complex 1: genetics /
Glucose: metabolism / Acetyl-CoA Carboxylase: metabolism /
Acetyl-CoA Carboxylase: genetics / Humans / Adaptor
Proteins, Signal Transducing: metabolism / Adaptor Proteins,
Signal Transducing: genetics / Fatty Acids: metabolism /
Animals / Cell Survival / Cell Cycle Proteins: metabolism /
Cell Cycle Proteins: genetics / Mice / NADP: metabolism /
Protein Biosynthesis / Phosphoproteins: metabolism /
Phosphoproteins: genetics / Oxidative Stress / Cell Line,
Tumor / Eukaryotic Initiation Factors: metabolism /
Eukaryotic Initiation Factors: genetics},
cin = {A410 / B410 / HD01 / ED01},
ddc = {500},
cid = {I:(DE-He78)A410-20160331 / I:(DE-He78)B410-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)ED01-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38744825},
doi = {10.1038/s41467-024-48386-y},
url = {https://inrepo02.dkfz.de/record/290199},
}