beta-Thymosins.
The development of thymosin beta(4) from a thymic hormone to an actin-sequestering peptide and back to a cytokine supporting wound healing will be outlined. Thymosin fraction 5 consists of a mixture of polypeptides and improves immune response. Starting with fraction 5, several main peptides (thymosin alpha(1), polypeptide beta(1), and thymosin beta(4)) were isolated and tested for biological activity. However, none of the isolated peptides were really thymic hormones. They are all biological important peptides with diverse functions. Polypeptide beta(1) is identical to ubiquitin truncated by two C-terminal glycine residues. Several peptides related to thymosin beta(4) were isolated and sequenced from various species. Large amounts of thymosin beta(4) were found in many cells. It was postulated that the beta-thymosins might have a general function. The identification of a biological function of thymosin beta(4) was tedious. In 1990, Dan Safer and his colleagues recognized that thymosin beta(4) sequesters G-actin. The dissociation constant of the complex in the micromolar range allows for fast binding and release of G-actin. beta-Thymosins are the main intracellular G-actin-sequestering peptides in most vertebrate cells. Thymosin beta(4) is unstructured but folds into a stable conformation on binding to G-actin. It is present in the nucleus as well as the cytoplasm and might be responsible for sequestering nuclear actin. Several biological effects are attributed to thymosin beta(4), oxidized thymosin beta(4), or to ac-SDKP possibly generated from thymosin beta(4). However, very little is known about molecular mechanisms mediating the effects attributed to extracellular beta-thymosins.
Hannappel
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Institute of Biochemistry, University of Erlangen-Nuremberg Fahrstr. 17, 91054 Erlangen, Germany. eh@biochem.uni-erlangen.de
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D000099201:Thymosin beta(4)
D013947:Thymosin; D000099201:Thymosin beta(4)