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真核细胞对外界压力刺激会做出一系列应答反应,如暂停蛋白质翻译系统,从而使细胞能更好地适应环境压力。通过应激颗粒(stress granules,SG)的形成包裹未被翻译的mRNA是该适应性调节的重要方式。研究表明,环境压力导致eIF2α上游激酶的激活从而磷酸化eIF2α,翻译起始受阻,随后,TIA-1、TTP等蛋白迅速与mRNP结合聚集成SG,并在微管蛋白的帮助下进一步向细胞核聚集,形成成熟的SG。当压力消失,SG依赖微管及其动力蛋白进行解聚,释放包裹的mRNA及蛋白。细胞内成熟的SG在转录后调节中发挥重要作用,并且通过其组成蛋白在肿瘤凋亡、病毒侵染、免疫、炎症反应及由蛋白错误折叠引起的疾病中发挥作用。该文首次综述了压力颗粒研究进展,为充分认识SG的病理生理性调节功能提供参考。
Eukaryotic cells respond to external stress to make a series of response, such as the suspension of the protein translation system, so that cells can better adapt to environmental stress. Encapsulation of untranslated mRNA by the formation of stress granules (SG) is an important way for this adaptive regulation. Studies have shown that environmental stress leads to the activation of eIF2α upstream kinase to phosphorylate eIF2α, and the initiation of translation is blocked. Subsequently, proteins such as TIA-1 and TTP rapidly aggregate with mRNP to form SG, and further to the nucleus with the help of tubulin , Forming a mature SG. When the pressure disappears, SG relies on microtubules and their dynein to depolymerize and release the encapsulated mRNA and protein. The maturation of SG plays an important role in post-transcriptional regulation and through its constitutive proteins play a role in tumor apoptosis, viral infection, immunity, inflammatory response and diseases caused by protein misfolding. This review summarizes the research progress of pressure particles for the first time and provides a reference for fully understanding the pathophysiological regulation of SG.