title: Small changes huge impact: the role of thioredoxin 1 in the regulation of apoptosis by S-nitrosylation.
abstract: Nitric oxide (NO) is a bioregulator of apoptosis, which has both antiapoptotic and proapoptotic functions. However, the molecular mechanisms responsible for its opposite biological effects are not fully understood. Recent advances in the study of protein S-nitrosylation may provide novel insights into the regulation of apoptotic signaling by NO. S-nitrosylation of some proteins, such as glyceraldehyde-3-phosphate dehydrogenase and Fas, stimulates apoptosis whereas S-nitrosylation of other proteins, such as caspases and Bcl-2, inhibits apoptosis, implying the complexity of the biological function of this post-translational modification. Moreover, the nitrosylation and denitrosylation can be regulated by the thioredoxin 1 (Trx1) system. Studies have shown that Trx1 either transnitrosylates or denitrosylates specific proteins, depending on the redox status of different cysteine residues in Trx1. The Cys73 of S-nitrosylated Trx1 is responsible for its transnitrosylating activity whereas the free thiol in Cys32 of Trx1 for its denitrosylating activity. In this minireview, we provide an overview in the understanding of the interactions between Trx1 and the NO targets, and discuss the role of Trx1-mediated S-nitrosylation and denitrosylation of specific proteins in regulating apoptosis.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. lihl@sjtu.edu.cn
authors.forename: Huili
authors.initials: H
authors.lastname: Li
authors.forename: Ajun
authors.initials: A
authors.lastname: Wan
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.forename: Dequan
authors.initials: D
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis; D020134:Catalytic Domain; D003545:Cysteine / Q000378:metabolism; D005786:Gene Expression Regulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013879:Thioredoxins / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D009569:Nitric Oxide; D013879:Thioredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003545:Cysteine; D009584:Nitrogen