Institute of Functional Biology and Genomics (IBFG), University of Salamanca-CSIC, Zacarias Gonzalez 2, 37007 Salamanca, Spain.
Biochem J. 2013 Jun 15;452(3):e7-9. doi: 10.1042/BJ20130560.
Besides the necessary changes in the expression of cell cycle-related proteins, cancer cells undergo a profound series of metabolic adaptations focused to satisfy their excessive demand for biomass. An essential metabolic transformation of these cells is increased glycolysis, which is currently the focus of anticancer therapies. Several key players have been identified, so far, that adapt glycolysis to allow an increased proliferation in cancer. In this issue of the Biochemical Journal, Novellasdemunt and colleagues elegantly identify a novel mechanism by which MK2 [MAPK (mitogen-activated protein kinase)-activated protein kinase 2], a key component of the MAPK pathway, up-regulates glycolysis in response to stress in cancer cells. The authors found that, by phosphorylating specific substrate residues, MK2 promotes both increased the gene transcription and allosteric activation of PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), a key glycolysis-promoting enzyme. These results reveal a novel pathway through which MK2 co-ordinates metabolic adaptation to cell proliferation in cancer and highlight PFKFB3 as a potential therapeutic target in this devastating disease.
除了细胞周期相关蛋白表达的必要变化外，癌细胞还经历了一系列深刻的代谢适应，以满足其对生物量的过度需求。这些细胞的一种重要代谢转化是糖酵解增加，目前这是抗癌治疗的重点。迄今为止，已经确定了几个关键的参与者，它们使糖酵解适应以允许癌细胞的增殖增加。在本期《生物化学杂志》中，Novellasdemunt 及其同事巧妙地确定了一种新的机制，即 MAPK（丝裂原激活蛋白激酶）途径中的关键组成部分 MK2 [丝裂原激活蛋白激酶激活的蛋白激酶 2] 通过该机制响应癌细胞应激而上调糖酵解。作者发现，通过磷酸化特定的底物残基，MK2 促进了关键的糖酵解促进酶 PFKFB3（6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 3）的基因转录和变构激活。这些结果揭示了一条新的途径，通过该途径，MK2 协调了癌症中细胞增殖的代谢适应，并强调了 PFKFB3 作为这种毁灭性疾病的潜在治疗靶点。
