Thymosin beta4 and its posttranslational modifications.

Thymosin beta(4) as well as the other members of the beta-thymosin family are important G-actin sequestering peptides. The chemical properties, the biosynthesis, and posttranslational modifications (PTMs) of these peptides are discussed. During biosynthesis of thymosin beta(4) the initiator methionine is removed and the N-terminus is acetylated. Research on proteomics revealed several acetylated lysine residues and two phosphorylated threonine residues. The enormous number of phosphorylable and acetylable sites in the human proteome raises the question about the biological significance of these PTMs in the context of beta-thymosins. Presently, this question cannot be answered because neither the concentration of these modified beta-thymosins in cells is known nor the consequences of the modifications on the biological function(s) of beta-thymosins have been studied yet. Thymosin beta(4) is also posttranslationally modified by transglutaminase forming covalent bonds with other molecules. Prolyl oligopeptidase generates ac-SDKP from thymosin beta(4). The concentration of C-terminal peptide fragments of thymosin beta(4) is elevated in the blood of patients with rheumatoid arthritis.