S-nitrosylation: Physiological regulation of NF-κB

摘要

A spate of recent discoveries indicates that the study of protein S-nitrosylation is rapidly leaving its salad days behind. S-nitrosylation, the formation of S-nitrosothiol (SNO) by covalent addition to cysteine (Cys) residues of a nitric oxide (NO) moiety (formally as NO~+), has been shown to regulate in intact cells the function of a broad spectrum of proteins (1). Important recent findings include demonstrations of major roles for S-nitrosylation in vesicle-mediated insulin release (2), in protein processing associated with the neurode-generation of Parkinson's disease (3), and in the essential mechanisms of vectorial membrane trafficking (4). In this issue of PNAS, Reynaert et al. (5) lend a hand in the unveiling of S-nitrosylation as it operates in cellular context by elucidating a role in regulating NF-κB. NF-κB denotes a ubiquitous family of transcription factors that transduce a wide range of noxious or inflammatory stimuli into the coordinated activation of multiple genes, including those coding for cytokines, cytokine receptors, adhesion molecules, and antiapo-ptotic proteins (6). NF-κB thus serves as a critical element in immune and inflammatory responses and in cell survival and proliferation, with central roles in host defense and in acute and chronic disorders of immune function. NF-κB can up-regulate the expression of all major NO synthases (nNOS, iNOS, and eNOS).