Hannappel E
Institute of Biochemistry, University of Erlangen-Nuremberg Fahrstr. 17, 91054 Erlangen, Germany.
Ann N Y Acad Sci. 2007 Sep;1112:21-37. doi: 10.1196/annals.1415.018. Epub 2007 Apr 27.
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.
本文将概述胸腺素β4从一种胸腺激素发展成为一种肌动蛋白隔离肽，再回归为一种支持伤口愈合的细胞因子的过程。胸腺素组分5由多种多肽混合而成，可增强免疫反应。从组分5开始，几种主要的肽（胸腺素α1、多肽β1和胸腺素β4）被分离出来并测试其生物活性。然而，分离出的这些肽都并非真正的胸腺激素。它们都是具有多种功能的重要生物肽。多肽β1与截去两个C末端甘氨酸残基的泛素相同。从不同物种中分离并测序了几种与胸腺素β4相关的肽。在许多细胞中都发现了大量的胸腺素β4。据推测，β-胸腺素可能具有普遍功能。确定胸腺素β4的生物学功能是一项繁琐的工作。1990年，丹·萨弗尔及其同事认识到胸腺素β4能隔离G-肌动蛋白。该复合物在微摩尔范围内的解离常数允许G-肌动蛋白快速结合和释放。β-胸腺素是大多数脊椎动物细胞中主要的细胞内G-肌动蛋白隔离肽。胸腺素β4无特定结构，但在与G-肌动蛋白结合时会折叠成稳定的构象。它存在于细胞核和细胞质中，可能负责隔离核肌动蛋白。胸腺素β4、氧化型胸腺素β4或可能由胸腺素β4产生的乙酰化的DKP具有多种生物学效应。然而，对于介导细胞外β-胸腺素相关效应的分子机制知之甚少。
