Emerging Roles of Cell Cycle Regulators in Adipocyte Metabolism

Cells can adapt their growth and metabolism to their needs and the extracellular signals they receive. Some stimuli, such as stress or nutrients, are not only proliferative but also metabolic signals, suggesting a close crosstalk between these two biological processes. Indeed, the response to a metabolic signal can require the activation of transcription factors and of signaling molecules that result in the inhibition of cell cycle progression and ultimately cell proliferation. The cell cycle is a finely tuned process (Fig. 2.1) the progression of which is orchestrated by holoenzymes that are composed of regulatory subunits (i.e., cyclins) and catalytic subunits, i.e., cyclin-dependent kinases (Cdks). Cdks, which belong to the family of the serine/threonine kinases, are activated by phosphorylation and dephosphorylation events and interact with specific cyclins to form heterodimers (Malumbres and Barbacid 2005). The cyclin D-Cdk4 and cyclin D-Cdk6 complexes act during the G1 phase, whereas the cyclin E-Cdk2 complex regulates the G1/S transition. The main substrates of the cyclin-Cdk complexes are proteins of the retinoblastoma (known also as «pocket protein») family (i.e., pRb, p107 and p130) that regulate the G1/S transition of the cell cycle. Phosphorylation of retinoblastoma proteins by cyclin-Cdk complexes