An essential role of N-terminal arginylation in cardiovascular development

被引：260

作者：

Kwon, YT ^{[1
]}

Kashina, AS ^{[1
]}

Davydov, IV ^{[1
]}

Hu, RG ^{[1
]}

An, JY ^{[1
]}

Seo, JW ^{[1
]}

Du, F ^{[1
]}

Varshavsky, A ^{[1
]}

机构：

[1] CALTECH, Div Biol, Pasadena, CA 91125 USA

来源：

SCIENCE | 2002年 / 297卷 / 5578期

关键词：

D O I：

10.1126/science.1069531

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：96 / 99

页数：5

共 28 条

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