Glucose and glutamine metabolism control by APC and SCF during the G1-to-S phase transition of the cell cycle

• Autores: Irving Omar Estévez-García, Verónica Cordoba-Gonzalez, Eleazar Lara Padilla, Abel Fuentes-Toledo, Ramcés Falfán Valencia, Rafael Campos Rodríguez, E. Abarca Rojano
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 70, Nº. 2, 2014 (Ejemplar dedicado a: Special Section on the CTP network: Original papers from the 10th meeting of the CTPIOD (Contribution To Progress in Obesity and Diabetes Research), 22th of May 2013, Reus, Spain.), págs. 569-581
• Idioma: inglés
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• Resumen

  • Recent studies have given us a clue as to how modulations of both metabolic pathways and cyclins by the ubiquitin system influence cell cycle progression. Among these metabolic modulations, an aerobic glycolysis and glutaminolysis represent an initial step for metabolic machinery adaptation. The enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and glutaminase-1 (GLS1) maintain a high abundance in glycolytic intermediates (for synthesis of non-essential amino acids, the use of ribose for the synthesis of nucleotides and hexosamine biosynthesis), as well as tricarboxylic acid cycle intermediates (replenishing the loss of mitochondrial citrate), respectively. On the one hand, regulation of these key metabolic enzymes by ubiquitin ligases anaphase-promoting complex/cyclosome (APC/C) and Skp1/cullin/F-box (SCF) has revealed the importance of anaplerosis by both glycolysis and glutaminolysis to overcome the restriction point of the G1 phase by maintaining high levels of glycolytic and glutaminolytic intermediates. On the other hand, only glutaminolytic intermediates are necessary to drive cell growth through the S and G2 phases of the cell cycle. It is interesting to appreciate how this reorganization of the metabolic machinery, which has been observed beyond cellular proliferation, is a crucial determinant of a cell�s decision to proliferate. Here, we explore a unifying view of interactions between the ubiquitin system, metabolic activity, and cyclin-dependent kinase complexes activity during the cell cycle.