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Review
. 2017 Nov 10:8:311.
doi: 10.3389/fendo.2017.00311. eCollection 2017.

E2F1, a Novel Regulator of Metabolism

Pierre-Damien Denechaud  1 , Lluis Fajas  1 , Albert Giralt  1
Affiliations
Review

E2F1, a Novel Regulator of Metabolism

Pierre-Damien Denechaud et al. Front Endocrinol (Lausanne). .

Abstract

In the past years, several lines of evidence have shown that cell cycle regulatory proteins also can modulate metabolic processes. The transcription factor E2F1 is a central player involved in cell cycle progression, DNA-damage response, and apoptosis. Its crucial role in the control of cell fate has been extensively studied and reviewed before; however, here, we focus on the participation of E2F1 in the regulation of metabolism. We summarize recent findings about the cell cycle-independent roles of E2F1 in various tissues that contribute to global metabolic homeostasis and highlight that E2F1 activity is increased during obesity. Finally, coming back to the pivotal role of E2F1 in cancer development, we discuss how E2F1 links cell cycle progression with different metabolic adaptations required for cell growth and survival.

Keywords: E2F1; cancer metabolism; cell cycle regulators; metabolic diseases; obesity.

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Figures

Figure 1
Figure 1
Main roles of E2F1 in metabolic tissues. E2F1 participates in the differentiation of several tissues, but also in the regulation of specific metabolic functions in fully differentiated organs, thus contributing to global metabolic homeostasis. Moreover, during obesity, E2F1 activity is increased and it contributes to some of the comorbidities of this pathological condition. Pathways activated by E2F1 are represented in green while pathways repressed by E2F1 are in red.
Figure 2
Figure 2
E2F1 contributes to the Warburg effect. E2F1 participates in the characteristic aerobic glycolysis observed in many tumors by different mechanisms. E2F1 promotes glycolysis by repressing the expression of Sirtuin 6 (Sirt6), a negative regulator of glycolytic gene expression and by promoting the expression of the F-type isoform of 6-phosphofructo-2-kinase/fructose-2,6-bissphosphatase (PFKB). E2F1 also recruits a Pontin/Reptin complex to promote the expression of genes involved in glycolysis and lactate export. Additionally, E2F1 blocks glucose oxidation in the mitochondria by promoting the expression of pyruvate dehydrogenase kinase (PDK) enzymes, which inhibit the pyruvate dehydrogenase complex (PDH).
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