期刊
NATURE CELL BIOLOGY
卷 13, 期 9, 页码 1146-U184出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2309
关键词
-
类别
资金
- Agence Nationale pour la Recherche (ANR genopath)
- INSERM-Association pour la Recherche sur le Diabete (PNR Diabete)
- Association Francaise des Diabetiques
- Societe Francophone du Diabete
- Association pour la Recherche contre le Cancer
- Fondation pour la Recherche Medicale
- Ligue Contre le Cancer
- European Research Council
- National Institutes of Health
- Swiss National Science Foundation
- EPFL
- Ministere de l'Enseignement Superieur et de la Recherche
- Agence Nationale pour la Recherche
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(1). E2F transcription factors regulate both proliferative and metabolic genes(2,3). E2Fs have been implicated in the G1/S cell-cycle transition, DNA repair, apoptosis, development and differentiation(2-4). In pancreatic beta-cells, E2F1 gene regulation facilitated glucose-stimulated insulin secretion(5,6). Moreover, mice lacking E2F1 (E2f1(-/-)) were resistant to diet-induced obesity(4). 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据