Glutaredoxin: role in reversible protein s-glutathionylation and regulation of redox signal transduction and protein translocation.
Reversible posttranslational modifications on specific amino acid residues can efficiently regulate protein functions. O-Phosphorylation is the prototype and analogue to the rapidly emerging mechanism of regulation known as S-glutathionylation. The latter is being recognized as a potentially widespread form of modulation of the activities of redox-sensitive thiol proteins, especially those involved in signal transduction pathways and translocation. The abundance of reduced glutathione in cells and the ready conversion of sulfenic acids and S-nitroso derivatives to S-glutathione mixed disulfides support the notion that reversible S-glutathionylation is likely to be the preponderant mode of redox signal transduction. The glutaredoxin enzyme has served as a focal point and important tool for evolution of this regulatory mechanism because of its characterization as a specific and efficient catalyst of protein-SSG de-glutathionylation (akin to phosphatases). Identification of specific mechanisms and enzyme(s) that catalyze formation of protein-SSG intermediates, however, is largely unknown and represents a prime objective for furthering understanding of this evolving mechanism of cellular regulation. Several proteomic approaches, including the use of cysteine-reactive fluorescent and radiolabel probes, have been developed to detect arrays of proteins whose cysteine residues are modified in response to oxidants, thus identifying them as potential interconvertible proteins to be regulated by redox signaling (glutathionylation). Specific criteria were used to evaluate current data on cellular regulation via S-glutathionylation. Among many proteins under consideration, actin, protein tyrosine phosphatase-1B, and Ras stand out as the best current examples for establishing this regulatory mechanism.
Shelton
Melissa D
MD
Department of Pharmacology, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106-4965, USA.
Chock
P Boon
PB
Mieyal
John J
JJ
D000818:Animals; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D015398:Signal Transduction
D054477:Glutaredoxins; D010088:Oxidoreductases; D005978:Glutathione