Two domains of cell behavior—protein modification by nitric oxide (NO) and ubiquitin-dependent protein destruction by the N-end rule pathway—have been united by Rong-Gui Hu, Jun Sheng, Alexander Varshavsky, and colleagues (Caltech, Pasadena, CA). They find that NO oxidizes NH2-terminal cysteines on certain proteins, thus marking them for future destruction. NO could therefore act as a very spatially and temporally delimited source of a destruction signal.
Cysteine was already known to be destabilizing when present as an NH2-terminal residue, and there were hints that its oxidation might be involved. The Caltech group now find that oxidation is essential to make the cysteine a substrate for arginyl transferase. The arginylated protein is then destroyed by the rest of the N-end rule pathway.
One substrate of this pathway is shown to be the GTPase-activating protein RGS4. It is no longer arginylated and is more abundant in vivo when either arginyl transferase is deleted or NO levels are reduced pharmacologically. Two other RGS proteins are also substrates, and ∼30 uncharacterized proteins are candidates.
NO's short half-life, says Varshavsky, gives you the possibility of regulating proteins through on a subcellular level. NO-related drugs for regulating blood vessels and heart function may become more specific if they could be targeted to the N-end rule's part of NO signaling. 
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