title: New insights into the posttranslational regulation of human cytosolic thioredoxin by S-palmitoylation.
abstract: High level of palmitate is associated with metabolic disorders. We recently showed that enhanced level of S-palmitoylated cytosolic thioredoxin (Trx1) in mouse liver was new characteristic feature of insulin resistance. However, our understanding of the effect of S-palmitoylation on Trx1 is limited, and the tissue specificity of Trx1 S-palmitoylation is unclear. Here we show that S-palmitoylation also occurs at Cys73 of Trx1 in living endothelial cells, and the level of S-palmitoylated Trx1 undergoes regulation by insulin signaling. Trx1 prefers thiol-thioester exchange with palmitoyl-CoA to acetyl-CoA. S-palmitoylation alters conformation or secondary structure of Trx1, as well as decreases the ability of Trx1 to transfer electrons from thioredoxin reductase to S-nitrosylated protein-tyrosine phosphatase 1B and S-nitroso-glutathione. Our results demonstrate that S-palmitoylation is an important post-translational modification of human Trx1.
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, YuQuan Road 19(A), 100049 Beijing, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, YuQuan Road 19(A), 100049 Beijing, China. Electronic address: liazho@ucas.ac.cn.
authors.forename: Liangwei
authors.initials: L
authors.lastname: Zhong
mesh_terms: D002460:Cell Line; D002942:Circular Dichroism; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D019308:Palmitic Acid / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D013050:Spectrometry, Fluorescence; D053719:Tandem Mass Spectrometry; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019308:Palmitic Acid; D013879:Thioredoxins
keywords: Insulin; PTP1B; Posttranslational modification; S-palmitoylation; Thioredoxin