The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase

► ECS(SPSB) interacts with iNOS, but not nNOS and eNOS. ► ECS(SPSB) induces the proteasomal degradation of iNOS, but not of nNOS and eNOS. ► CHIP does not interact with iNOS. ► CHIP does not induce the proteasomal degradation of iNOS. ► The lifetime of the unbound form of iNOS to ECS(SPSB) is extended in macrophages.