Edison Biotechnology Institute and Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA.
Free Radic Biol Med. 2011 Jun 15;50(12):1717-25. doi: 10.1016/j.freeradbiomed.2011.03.032. Epub 2011 Apr 2.
Generation of nitric oxide (NO(•)) can upstream induce and downstream mediate the kinases that phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF2α), which plays a critical role in regulating gene expression. There are four known eIF2α kinases (EIF2AKs), and NO(•) affects each one uniquely. Whereas NO(•) directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of l-arginine, which is used by nitric oxide synthase (NOS) during the production of NO(•). Finally EIF2AK2 (PKR), which can mediate inducible NOS expression and therefore NO(•) production, can also be activated by NO(•). The production of NO(•) and activation of EIF2AKs coordinately regulate physiological and pathological events such as innate immune response and cell apoptosis.
一氧化氮（NO(•)）的产生可以在上游诱导并在下游调节使真核起始因子 2（eIF2α）的α亚基磷酸化的激酶，该激酶在调节基因表达中起着关键作用。有四种已知的 eIF2α 激酶（EIF2AKs），而 NO(•) 对每种激酶的影响都是独特的。虽然 NO(•) 直接激活 EIF2AK1（HRI），但它间接激活 EIF2AK3（PERK）。EIF2AK4（GCN2）的激活是由于 l-精氨酸的消耗，而 l-精氨酸是在产生 NO(•) 期间由一氧化氮合酶（NOS）使用的。最后，EIF2AK2（PKR）可以介导诱导型 NOS 的表达，因此也可以被 NO(•) 激活。NO(•) 的产生和 EIF2AKs 的激活共同调节生理和病理事件，如先天免疫反应和细胞凋亡。
