Silva Ricardo L A, Wendel Hans Guido
Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cell Cycle. 2008 Mar 1;7(5):553-5. doi: 10.4161/cc.7.5.5486. Epub 2007 Dec 21.
Deregulation of protein translation is a common event in cancer and occurs frequently as a result of mutational activation of the AKT signaling pathway. We had previously reported the in vivo oncogenic activity of the translation initiation factor eIF4E, which acts downstream AKT and mTOR. We now identified an absolute requirement for Ser209 phosphorylation by the MNK1/2 kinases for eIF4E's oncogenic action. MNK1/2 kinases are dispensable for normal development in mammals. This potential difference between normal and cancer cells may provide a therapeutic avenue for targeting translational requirements in cancer.
蛋白质翻译失调是癌症中的常见现象,常因AKT信号通路的突变激活而频繁发生。我们之前报道过翻译起始因子eIF4E的体内致癌活性,它在AKT和mTOR下游发挥作用。我们现在发现,MNK1/2激酶对Ser209的磷酸化是eIF4E致癌作用的绝对必要条件。MNK1/2激酶对哺乳动物的正常发育并非必需。正常细胞与癌细胞之间的这种潜在差异可能为针对癌症中的翻译需求提供一条治疗途径。