Wortham Noel C, Stewart Joanna D, Harris Sean, Coldwell Mark J, Proud Christopher G
Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
Biochem J. 2016 Mar 1;473(5):571-80. doi: 10.1042/BJ20150828. Epub 2015 Nov 27.
The eukaryotic translation initiation factor eIF2B is a multi-subunit complex with a crucial role in the regulation of global protein synthesis in the cell. The complex comprises five subunits, termed α through ε in order of increasing size, arranged as a heterodecamer with two copies of each subunit. Regulation of the co-stoichiometric expression of the eIF2B subunits is crucial for the proper function and regulation of the eIF2B complex in cells. We have investigated the control of stoichiometric eIF2B complexes through mutual stabilization of eIF2B subunits. Our data show that the stable expression of the catalytic eIF2Bε subunit in human cells requires co-expression of eIF2Bγ. Similarly, stable expression of eIF2Bδ requires both eIF2Bβ and eIF2Bγ+ε. The expression of these subunits decreases despite there being no change in either the levels or the translation of their mRNAs. Instead, these subunits are targeted for degradation by the ubiquitin-proteasome system. The data allow us to propose a model for the formation of stoichiometric eIF2B complexes which can ensure their stoichiometric incorporation into the holocomplex.
真核生物翻译起始因子eIF2B是一种多亚基复合物，在细胞全局蛋白质合成的调控中起着关键作用。该复合物由五个亚基组成，按大小递增顺序称为α至ε，每个亚基有两个拷贝，排列成异源十聚体。eIF2B亚基化学计量表达的调控对于细胞中eIF2B复合物的正常功能和调控至关重要。我们通过eIF2B亚基的相互稳定作用研究了化学计量eIF2B复合物的控制。我们的数据表明，催化性eIF2Bε亚基在人细胞中的稳定表达需要eIF2Bγ的共表达。同样，eIF2Bδ的稳定表达需要eIF2Bβ以及eIF2Bγ + ε。尽管这些亚基的mRNA水平或翻译没有变化，但其表达仍会降低。相反，这些亚基被泛素 - 蛋白酶体系统靶向降解。这些数据使我们能够提出一个化学计量eIF2B复合物形成的模型，该模型可以确保它们以化学计量方式掺入全复合物中。
