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...
