Tuning Specific Translation in Cancer Metastasis and Synaptic Memory: Control at the MNK-eIF4E Axis

被引:77
作者
Bramham, Clive R. [1 ,2 ]
Jensen, Kirk B. [3 ,4 ]
Proud, Christopher G. [3 ,4 ]
机构
[1] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway
[2] Univ Bergen, KG Jebsen Ctr Neuropsychiat Disorders, N-5009 Bergen, Norway
[3] South Australian Hlth & Med Res Inst, Adelaide, SA 5000, Australia
[4] Univ Adelaide, Sch Biol Sci, Adelaide, SA 5005, Australia
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
INITIATION-FACTOR; 4E; FRAGILE-X-SYNDROME; KINASE-INTERACTING KINASES; ACTIVATED PROTEIN-KINASE; MESSENGER-RNA TRANSLATION; LONG-TERM POTENTIATION; EIF4E PHOSPHORYLATION; LOCAL TRANSLATION; N-TERMINI; C-TERMINI;
D O I
10.1016/j.tibs.2016.07.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The eukaryotic translation initiation factor (eIF) 4E, which binds to the 5'-cap of mRNA, undergoes phosphorylation on a single conserved serine, executed by the mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). However, the functional consequences and physiological roles of MNK signalling have remained obscure. Now, new pharmacological and genetic tools have provided unprecedented insights into the function of MNKs and eIF4E phosphorylation. The studies suggest that MNKs control the translation of specific mRNAs in cancer metastasis and neuronal synaptic plasticity by a novel mechanism involving the regulation of the translational repressor, cytoplasmic fragile - X protein-interacting protein 1 (CYFIP1). These recent breakthroughs go a long way to resolving the longstanding enigma and controversy surrounding the function of the MNK-eIF4E axis in cancer cell biology and neurobiology.
引用
收藏
页码:847 / 858
页数:12
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