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

Journal of Physiology and Biochemistry - Tập 70 - Trang 569-581 - 2014
Irving Omar Estévez-García1, Verónica Cordoba-Gonzalez1, Eleazar Lara-Padilla1, Abel Fuentes-Toledo1, Ramcés Falfán-Valencia2, Rafael Campos-Rodríguez1, Edgar Abarca-Rojano1,3
1Instituto Politecnico Nacional, Escuela Superior de Medicina, Seccion de Estudios de Posgrado e Investigacion, México City, Mexico
2Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, México City, Mexico
3Laboratorio de Respiracion Celular, Instituto Politecnico Nacional, Escuela Superior de Medicina, Seccion de Estudios de Posgrado e Investigacion, Mexico D.F., Mexico

Tóm tắt

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.

Tài liệu tham khảo

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