Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.

Nitric oxide: a regulator of eukaryotic initiation factor 2 kinases.
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DOI:
10.1016/j.freeradbiomed.2011.03.032
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发表时间:
2011-06-15
影响因子:
7.4
通讯作者:
Wu, Shiyong
Wu, Shiyong
中科院分区:
医学1区
文献类型:
--
作者:
Tong, Lingying;Heim, Rachel A.;Wu, Shiyong

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一氧化氮 (NO•) 的生成可以在上游诱导并在下游介导磷酸化真核起始因子 2 (eIF2α) α 亚基的激酶,该激酶在调节基因表达中发挥着关键作用。有四种已知的 eIF2α 激酶 (EIF2AK),NO• 对每一种都有独特的影响。 NO• 直接激活EIF2AK1 (HRI),而它间接激活EIF2AK3 (PERK)。 EIF2AK4 (GCN2) 通过消耗 L-精氨酸而被激活,L-精氨酸在 NO• 的产生过程中使用一氧化氮合酶 (NOS)。最后,EIF2AK2 (PKR) 可以介导诱导型 NOS 表达,从而介导 NO• 的产生,也可以被 NO• 激活。 NO•的产生和EIF2AK的激活协调调节生理和病理事件,例如先天免疫反应和细胞凋亡。
Generation of nitric oxide (NO•) can upstream induce and downstream mediate the kinases that phosphorylate the alpha 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. While NO• directly activates EIF2AK1 (HRI), it indirectly activates EIF2AK3 (PERK). EIF2AK4 (GCN2) is activated by depletion of L-arginine, which is used 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.
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