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research article

E2F transcription factor-1 regulates oxidative metabolism

Blanchet, Emilie
•
Annicotte, Jean-Sébastien
•
Lagarrigue, Sylviane
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2011
Nature cell biology

Cells respond to stress by coordinating proliferative and metabolic pathways. Starvation restricts cell proliferative (glycolytic) and activates energy productive (oxidative) pathways. Conversely, cell growth and proliferation require increased glycolytic and decreased oxidative metabolism levels. E2F transcription factors regulate both proliferative and metabolic genes. E2Fs have been implicated in the G1/S cell-cycle transition, DNA repair, apoptosis, development and differentiation. In pancreatic β-cells, E2F1 gene regulation facilitated glucose-stimulated insulin secretion. Moreover, mice lacking E2F1 (E2f1(-/-)) were resistant to diet-induced obesity. Here, we show that E2F1 coordinates cellular responses by acting as a regulatory switch between cell proliferation and metabolism. In basal conditions, E2F1 repressed key genes that regulate energy homeostasis and mitochondrial functions in muscle and brown adipose tissue. Consequently, E2f1(-/-) mice had a marked oxidative phenotype. An association between E2F1 and pRB was required for repression of genes implicated in oxidative metabolism. This repression was alleviated in a constitutively active CDK4 (CDK4(R24C)) mouse model or when adaptation to energy demand was required. Thus, E2F1 represents a metabolic switch from oxidative to glycolytic metabolism that responds to stressful conditions.

  • Details
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Type
research article
DOI
10.1038/ncb2309
Web of Science ID

WOS:000294487000021

Author(s)
Blanchet, Emilie
Annicotte, Jean-Sébastien
Lagarrigue, Sylviane
Aguilar, Victor
Clapé, Cyrielle
Chavey, Carine
Fritz, Vanessa
Casas, François
Apparailly, Florence
Auwerx, Johan  
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Date Issued

2011

Published in
Nature cell biology
Volume

13

Issue

9

Start page

1146

End page

52

Subjects

Activated-Receptor-Gamma

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Skeletal-Muscle

•

Adipocyte Differentiation

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Gene-Expression

•

Enzyme-Activity

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Pgc-1-Alpha

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Growth

•

Coactivator

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Repression

•

Protects

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LISP  
Available on Infoscience
November 15, 2011
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/72610
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