Publications

Latest publication 08/14/2011

E2F transcription factor-1 regulates oxidative metabolism-

Cells respond to stress by coordinating proliferative and metabolic pathways. Starvation restricts cell proliferative (glycolytic) and activates...

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    [title] => E2F transcription factor-1 regulates oxidative metabolism- 
    [paragraph] => E2F transcription factor-1 regulates oxidative metabolism. 
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Authors
E. Blanchet, J.-S. Annicotte, S. Lagarrigue, V. Aguilar, C. Clapé et al.

 Lab
IRCM, Institut de Recherche en Cancérologie, Montpellier France.
Journal
Nature Cell Biology
Abstract
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 _-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.
BIOSEB Instruments Used
Treadmill (BX-TM),Passive avoidance (LE870)

Keywords/Topics
Cell metabolism; Metabolism
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