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An Essential Role of N-Terminal Arginylation in Cardiovascular Development

Kwon, Yong Tae and Kashina, Anna S. and Davydov, Ilia V. and Hu, Rong-Gui and An, Jee Young and Seo, Jai Wha and Du, Fangyong and Varshavsky, Alexander (2002) An Essential Role of N-Terminal Arginylation in Cardiovascular Development. Science, 297 (5578). pp. 96-99. ISSN 0036-8075. doi:10.1126/science.1069531.

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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 mouseATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found thatATE1 −/− 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.

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Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 2002 American Association for the Advancement of Science. 3 January 2002; Accepted 5 June 2002. We thank D. Anderson, D. Shin, and Y. Mukouyama for helpful discussions; C. Brower for comments on the manuscript; S. Pease, B. Kennedy, and L. Sandoval for expert care of mice; G. Hathaway for sequencing of RGS4; N. Dinh and M. Young for mass spectrometry; and J. K. Yoon for pLacF. Supported by NIH grant GM31530 and a Kirsch Foundation grant to A.V.
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Kirsch FoundationUNSPECIFIED
Issue or Number:5578
Record Number:CaltechAUTHORS:20141114-160435229
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Official Citation:Kwon, Y. T., Kashina, A. S., Davydov, I. V., Hu, R.-G., An, J. Y., Seo, J. W., . . . Varshavsky, A. (2002). An Essential Role of N-Terminal Arginylation in Cardiovascular Development. Science, 297(5578), 96-99. doi: 10.1126/science.1069531
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51810
Deposited By: Joanne McCole
Deposited On:17 Nov 2014 21:40
Last Modified:10 Nov 2021 19:16

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