Participation of pRB-cdk4-E2F1 in lipogenesis and glycolysis

We want to prove that this pathway plays a central role in controlling glycolysis/gluconeogenesis and fatty acid synthesis, which depends on intermediates from glycolysis. We identify direct targets of this pathway using ChIP-seq analyses. Our data indicate that FAS, ELOVL6, SCD1 and Hexokinase could be E2F1 target genes, which we are validating with E2F1-/-, cdk4-/- mice. We generate adipose tissue- (for lipids) and liver-specific (for energy metabolism) conditional knockouts of E2F1-/- and cdk4-/- in mice. The metabolic phenotype of these mice will be extensively characterized. This includes, but is not limited to glucose homeostasis studies, lipids metabolism, and energy homeostasis analysis. Finally, we want to identify potential novel cdk4 targets involved in metabolism.

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