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Adapting to changes in nutrient availability and environmental conditions is a fundamental property of cells. This adaptation requires a multi-directional coordination between metabolism, growth, and the cell cycle regulators (consisting of the family of cyclin-dependent kinases (CDKs), their regulatory subunits known as cyclins, CDK inhibitors, the retinoblastoma family members, and the E2F transcription factors). Deciphering the mechanisms accountable for this coordination is crucial for understanding various patho-physiological processes. While it is well established that metabolism and growth affect cell division, this review will focus on recent observations that demonstrate how cell cycle regulators coordinate metabolism, cell cycle progression, and growth. We will discuss how the cell cycle regulators directly regulate metabolic enzymes and pathways and summarize their involvement in the endolysosomal pathway and in the functions and dynamics of mitochondria., (© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Specific cellular functions, such as proliferation, survival, growth, or senescence, require a particular adaptive metabolic response, which is fine tuned by members of the cell cycle regulators families. Currently, proteins such as cyclins, CDKs, or E2Fs are being studied in the context of cell proliferation and survival, cell signaling, cell cycle regulation, and cancer. We show in this review that cellular, animal and molecular studies provided enough evidence to prove that these factors play, in addition, crucial roles in the control of mitochondrial function; finally resulting in a dual proliferative and metabolic response., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We recently showed that the CDK4-pRB-E2F1 cell cycle regulators directly regulate the expression of Kir6.2, which is a key component of the K(ATP) channel involved in the regulation of glucose-induced insulin secretion. There is enough evidence to indicate that the CDK4-pRB-E2F1 regulatory pathway is involved in general glucose homeostasis, and metabolism. In this article we discuss which are the metabolic implications of these findings.

Regulation of peroxisome proliferator-activated receptor gamma (PPAR?) activity is the result of several events. The first control level is the regulation of the expression of PPAR?. Examples of this regulation, during adipogenesis, is the transactivation of the PPAR?promoter by transcription factors of the classical pathway, such as C/EBPs or ADD1/SREBP1, but also newly identified factors, such as E2Fs. When preadipocytes re-enter the cell cycle, PPAR?expression is induced coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. E2F1 induces PPAR?transcription during clonal expansion, whereas E2F4 represses PPAR?expression during terminal adipocyte differentiation. Hence, E2Fs represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPAR?expression. A second regulatory level of PPAR?action is interaction with cofactors. We will focus our attention on the atypical PPAR?modulators. We have described an interaction between PPAR?and the retinoblastoma protein, RB, which is both dependent upon ligand binding by PPAR?and upon the phosphorylation status of RB. The interaction between PPAR?and RB decreases the transcriptional activity of PPAR?through recruitment of the histone deacetylase HDAC3. Inhibition of HDAC activity consequently results in a strong activation of PPAR?.International Journal of Obesity (2005) 29, S10-S12. doi:10.1038/sj.ijo.0802906 [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 4 (CDK4) is a positive regulator of cell cycle progression, however, there is growing evidence demonstrating that its function exceeds the control of cell division. Here we show that CDK4 is an important regulator of cellular substrate utilization through direct inhibition of the metabolic regulator AMPK (AMP-activated protein kinase). [ABSTRACT FROM AUTHOR]