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Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations

机译:通过可逆赖氨酸氨基酰基感测和透射细胞内氨基酸信号

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摘要

Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intra-cellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the 3-amine of lysines in their substrates by producing reactive aminoacyl adenylates. The K-AA marks can be removed by deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that involved in deacetylation. These dynamically regulated K-AAs transduce signals of their respective amino acids. Reversible leucylation on ras-related GTP-binding protein A/B regulates activity of the mammalian target of rapamycin complex 1. Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks.
机译:氨基酸是已知的细胞信号和生理调节器,但它们如何在细胞内被感知尚不完全清楚。在此,我们报告了每一种氨酰-tRNA合成酶(ARS)通过催化其特定底物蛋白上赖氨酸氨基酰化(K-AA)的形成来感知其同源氨基酸的充足性。在生理水平上,氨基酸促进ARS与其底物结合,并通过产生反应性氨基酰腺苷酸在其底物中赖氨酸的3-胺上形成K-AAs。K-AA标记可以通过脱乙酰酶去除,如SIRT1和SIRT3,采用与脱乙酰化相同的机制。这些动态调节的K-AAs能传递各自氨基酸的信号。ras相关GTP结合蛋白A/B的可逆白细胞化调节雷帕霉素复合物1哺乳动物靶点的活性。细胞凋亡信号调节激酶1上的谷氨酰胺化抑制细胞凋亡。我们发现了ARSs的非标准功能,揭示了系统和功能性的氨基酸传感和信号转导网络。

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  • 来源
    《Cell metabolism》 |2018年第1期|共22页
  • 作者单位

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Chinese Acad Sci Inst Biochem &

    Cell Biol Shanghai Inst Biol Sci Shanghai 200031 Peoples R China;

    Chinese Acad Sci Inst Biochem &

    Cell Biol Shanghai Inst Biol Sci Shanghai 200031 Peoples R China;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Qinghai Univ Nationalities Key Lab Tibet Plateau Phytochem Qinghai Prov Coll Pharm Xining 810007;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

    Fudan Univ Obstet &

    Gynecol Hosp State Key Lab Genet Engn Sch Life Sci Shanghai 200032 Peoples;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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