Editors' ChoiceProtein Modifications

Taking Degradation to Heart

Science's STKE  09 Jul 2002:
Vol. 2002, Issue 140, pp. tw242-TW242
DOI: 10.1126/stke.2002.140.tw242

The ubiquitin pathway of protein degradation has gained prominence as a major regulatory network in mammalian cells. Arginine is commonly conjugated to the NH2-terminus of proteins during ubiquitin-dependent degradation, but the physiological functions of arginylation are unknown. Kwon et al. generated mice genetically deficient in one of the Arg-tRNA-protein transferases catalyzing this modification (ATE-1) and found that the embryos die from defects in heart development and angiogenesis. The authors also discovered a possible mechanism for the early cardiac defects: NH2-terminal cysteine is oxidized prior to its arginylation by ATE-1, suggesting that the NH2-terminal arginylation may function as an oxygen sensor.

Y. T. Kwon, A. S. Kashina, I. V. Davydov, R.-G. Hu, J. Y. An, J. W. Seo, F. Du, A. Varshavsky, An essential role of N-terminal arginylation in cardiovascular development. Science 296, 96-99 (2002). [Abstract] [Full Text]