Publication Date:
2002-07-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwon, Yong Tae -- Kashina, Anna S -- Davydov, Ilia V -- Hu, Rong-Gui -- An, Jee Young -- Seo, Jai Wha -- Du, Fangyong -- Varshavsky, Alexander -- GM31530/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):96-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12098698" target="_blank"〉PubMed〈/a〉
Keywords:
Alkylation
;
Aminoacyltransferases/*genetics/*metabolism
;
Animals
;
Aorta/embryology
;
Arginine/*metabolism
;
Aspartic Acid/metabolism
;
Blood Vessels/*embryology
;
Cell Line
;
Cysteic Acid/metabolism
;
Cysteine/metabolism
;
Female
;
Glutamic Acid/metabolism
;
Heart/*embryology
;
Heart Defects, Congenital/embryology
;
Heart Septal Defects/embryology
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Neovascularization, Physiologic
;
Oxidation-Reduction
;
Proteins/*metabolism
;
Pulmonary Artery/embryology
;
RGS Proteins/metabolism
;
Recombinant Proteins/metabolism
;
Sulfinic Acids/metabolism
;
Transcription Factors/metabolism
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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