Translational control by eIF5-miimc protein
|演題||Translational control by eIF5-miimc protein|
|講演者||Prof. Katsura Asano, Division of Biology, Kansas State
University, Manhattan, Kansas, U.S.A.
|場所||Seminar Room L13|
|内容||During translation initiation, the ribosome sets up the initiation complex on a start codon. In eukaryotes, this process is catalyzed by a myriad of proteins termed eukaryotic initiation factors (eIFs). It has been realized that a high stringency in selecting AUG as a start codon is governed by eIF1, eIF2, eIF3, and eIF5, which together form the multi-factor complex (MFC) carrying Met-tRNAi. eIF5-mimic protein (5MP) was discovered as a protein mimic of eIF5. Human encodes two copies of 5MP termed 5MP1 and 5MP2. In this talk, I describe biological functions of 5MP. First, quantitative mass spectroscropy analysis of 5MP associated proteins indicate that 5MP binds eIF1, eIF2 and eIF2 – an MFC-like complex – in human HEK293T cells. Second, 5MP overexpression induces ATF4 translation by inhibiting eIF2 and allowing the ribosome to overcome the inhibitor effect of upstream ORF (uORF) present in ATF4 leader region. Third, 5MP over expression increases the accuracy of initiation when excess copies eIF5 force the ribosome to mis-initiate from non-AUG codons. Forth, the knockdown of 5MP1 decreases growth of fibrosarcoma HT1080 in vivo. ATF4 is a transcription factor governing amino acid metabolism and apoptosis, and hence tumor survival. Translation initiation is reported to be less accurate in stem cells. We discuss the physiological roles of 5MP based on our findings.|
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