Ma Shuhua, Bhattacharjee Rumpa B, Bag Jnanankur
Department of Molecular and Cellular Biology, University of Guelph, Canada.
FEBS J. 2009 Jan;276(2):552-70. doi: 10.1111/j.1742-4658.2008.06803.x. Epub 2008 Dec 11.
Induction of heat shock proteins (HSPs) helps cells to survive severe hyperthermal stress and removes toxic unfolded proteins. At the same time, the cap-dependent translation of global cellular mRNA is inhibited, due to the loss of function of eukaryotic initiation factor (eIF)4F complex. It has been previously reported that, following heat shock, HSP27 binds to the insoluble granules of eIF4G and impedes its association with cytoplasmic poly(A)-binding protein (PABP) 1 and eIF4E. In the studies reported here, in addition to heat shock, we have included results of our investigation on the association between eIF4G, PABP1 and HSP27 during recovery from heat shock, when cap-dependent mRNA translation resumes. We showed here that in the heat-shocked cells, the PABP1-eIF4G complex dissociated, and both polypeptides translocated with the HSP27 to the nucleus. During recovery after heat shock, PABP1 and eIF4G were redistributed into the cytoplasm and colocalized with each other. In addition, PABP1 expression was upregulated and its translation efficiency was increased during the recovery period, possibly to meet additional demands on the translation machinery. HSP27 remained associated with the eIF4G-PABP1 complex during recovery from heat shock. Therefore, our results raise the possibility that the association of HSP27 with eIF4G may not be sufficient to suppress cap-dependent translation during heat shock. In addition, we provide evidence that the terminal oligopyrimidine cis-element of PABP1 mRNA is responsible for the preferential increase of PABP1 mRNA translation in cells undergoing recovery from heat shock.
热休克蛋白（HSPs）的诱导有助于细胞在严重热应激下存活，并清除有毒的未折叠蛋白。同时，由于真核起始因子（eIF）4F复合物功能丧失，全局细胞mRNA的帽依赖性翻译受到抑制。此前已有报道称，热休克后，HSP27与eIF4G的不溶性颗粒结合，并阻碍其与细胞质聚腺苷酸结合蛋白（PABP）1和eIF4E的结合。在本文报道的研究中，除了热休克外，我们还纳入了在热休克恢复过程中，当帽依赖性mRNA翻译恢复时，对eIF4G、PABP1和HSP27之间关联的研究结果。我们在此表明，在热休克细胞中，PABP1-eIF4G复合物解离，两种多肽与HSP27一起转运至细胞核。热休克后的恢复过程中，PABP1和eIF4G重新分布到细胞质中并相互共定位。此外，在恢复期间PABP1表达上调，其翻译效率增加，这可能是为了满足对翻译机制的额外需求。在热休克恢复过程中，HSP27仍与eIF4G-PABP1复合物结合。因此，我们的结果提出了一种可能性，即HSP27与eIF4G的结合可能不足以在热休克期间抑制帽依赖性翻译。此外，我们提供证据表明，PABP1 mRNA的末端寡嘧啶顺式元件负责热休克恢复细胞中PABP1 mRNA翻译的优先增加。
