Identification of a redox-modulatory interaction between selenoprotein W and 14-3-3 protein
| Autor: | Yeong Ha Jeon, Jea Hwang Lee, Ki Jun Park, Jun Ki Jang, Kwan Young Ko, Ick Young Kim |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cell signaling Amino Acid Motifs Mutation Missense Plasma protein binding Biology 03 medical and health sciences chemistry.chemical_compound Humans Binding site Phosphorylation Selenoproteins Molecular Biology 14-3-3 14-3-3 protein SelW Selenocysteine Selenoprotein W Cell Biology Hydrogen Peroxide Dithiothreitol Oxidative Stress 030104 developmental biology chemistry Biochemistry 14-3-3 Proteins MCF-7 Cells Female Thioredoxin Oxidation-Reduction Protein Binding |
| Zdroj: | Biochimica et biophysica acta. 1863(1) |
| ISSN: | 0006-3002 |
| Popis: | Selenoprotein W (SelW) contains a selenocysteine (Sec, U) in a conserved CXXU motif corresponding to the CXXC redox motif of thioredoxin, suggesting a putative redox function of SelW. We have previously reported that the binding of 14-3-3 protein to its target proteins, including CDC25B, Rictor and TAZ, is inhibited by the interaction of 14-3-3 protein with SelW. However, the binding mechanism is unclear. In this study, we sought to determine the binding site of SelW to understand the regulatory mechanism of the interaction between SelW and 14-3-3 and its biological effects. Phosphorylated Ser(pS) or Thr(pT) residues in RSXpSXP or RXXXp(S/T)XP motifs are well-known common 14-3-3-binding sites, but Thr41, Ser59, and T69 of SelW, which are computationally predicted to serve are phosphorylation sites, were neither phosphorylation sites nor sites involved in the interaction. A mutant SelW in which Sec13 is changed to Ser (U13S) was unable to interact with 14-3-3 protein and thus did not inhibit the interaction of 14-3-3 to other target proteins. However, other Cys mutants of SelW(C10S, C33S and C37S) normally interacted with 14-3-3 protein. The interaction of SelW to 14-3-3 protein was enhanced by diamide or H2O2 and decreased by dithiothreitol (DTT). Taken together, these findings demonstrate that the Sec of SelW is involved in its interaction with 14-3-3 protein and that this interaction is increased under oxidative stress conditions. Thus, SelW may have a regulatory function in redox cell signaling by interacting with 14-3-3 protein. |
| Databáze: | OpenAIRE |
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