Translational regulator eIF2α in tumor
Translational regulator eIF2α in tumor
复制标题
DOI：
10.1007/s13277-014-1789-0
复制
发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Q. Zheng;Jingjia Ye;Jiang Cao
中科院分区：
文献类型：
--
作者：
Q. Zheng;Jingjia Ye;Jiang Cao
真核生物翻译起始因子2α（eIF 2 α）是eIF 2的调节亚基，可被磷酸化失活。在对各种微环境胁迫的适应性反应中，eIF 2 α（p-eIF 2 α）被特异性激酶磷酸化显著下调蛋白质合成，同时选择性上调转录激活因子4（ATF 4）的翻译。ATF 4是一种转录激活因子，可以易位到细胞核中并上调参与氨基酸合成、氧化还原平衡、蛋白质成熟和降解的基因，从而导致自噬和凋亡的激活。在肿瘤进展过程中，适应性反应促进肿瘤细胞在严重应激下的存活和生长。因此，eIF 2 α磷酸化显著促进肿瘤进展和对治疗的抵抗。然而，也有证据表明p-eIF 2 α对肿瘤发生具有抑制作用。目前对eIF 2 α在肿瘤中的作用的认识还不完全，需要进一步研究。本文综述了eIF 2 α在肿瘤发生、发展、耐药和恶病质中的分子机制，以及eIF 2 α相关信号通路在肿瘤治疗中的应用前景。
The eukaryotic translation initiation factor 2α (eIF2α) is the regulatory subunit of eIF2 which can be inactivated by phosphorylation. In the adaptive response to various microenvironmental stresses, phosphorylation of eIF2α (p-eIF2α) by specific kinases significantly downregulates global protein synthesis while selectively upregulates the activating transcription factor 4 (ATF4) translation. The ATF4 is a transcription activator that can translocate into nucleus and upregulate genes involved in amino acid synthesis, redox balance, protein maturation, and degradation which lead to the activation of both autophagy and apoptosis. During tumor progression, adaptive response facilitates tumor cell survival and growth under severe stresses. Therefore, eIF2α phosphorylation significantly promotes tumor progression and resistance to therapy. However, there is also evidence showing that p-eIF2α exerts suppressive effects on tumorigenesis. Current understanding of the roles eIF2α plays in tumor is still incomplete and needs further investigation. This review addresses on the past and current efforts to delineate the molecular mechanisms of eIF2α in tumorigenesis, tumor progression, resistance to therapy, and tumor cachexia as well as the translational promise of therapeutic applications targeting eIF2α-related signaling pathway.