Kwon Yong Tae, Kashina Anna S, Davydov Ilia V, Hu Rong-Gui, An Jee Young, Seo Jai Wha, Du Fangyong, Varshavsky Alexander
Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Science. 2002 Jul 5;297(5578):96-9. doi: 10.1126/science.1069531.
The enzymatic conjugation of arginine to the N-termini of proteins is a part of the ubiquitin-dependent N-end rule pathway of protein degradation. In mammals, three N-terminal residues-aspartate, glutamate, and cysteine-are substrates for arginylation. The mouse ATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found that ATE1-/- embryos die with defects in heart development and in angiogenic remodeling of the early vascular plexus. Through biochemical analyses, we show that N-terminal cysteine, in contrast to N-terminal aspartate and glutamate, is oxidized before its arginylation by R-transferase, suggesting that the arginylation branch of the N-end rule pathway functions as an oxygen sensor.
精氨酸与蛋白质N端的酶促偶联是泛素依赖性蛋白质降解N端规则途径的一部分。在哺乳动物中，三种N端残基——天冬氨酸、谷氨酸和半胱氨酸——是精氨酸化的底物。小鼠ATE1基因编码一个精氨酸-tRNA-蛋白质转移酶（R-转移酶）家族，该家族介导N端精氨酸化。我们构建了缺乏ATE1的小鼠品系，发现ATE1基因敲除小鼠胚胎死于心脏发育缺陷和早期血管丛的血管生成重塑缺陷。通过生化分析，我们发现与N端天冬氨酸和谷氨酸不同，N端半胱氨酸在被R-转移酶精氨酸化之前被氧化，这表明N端规则途径的精氨酸化分支起到氧传感器的作用。
