Wang Haixia, Zhang Qiang, Zhu Dahai
Molecular and Cellular Developmental Biology Laboratory, Harbin Institute of Technology, 150001, Harbin, PR China.
Biochem Biophys Res Commun. 2003 Nov 28;311(4):877-83. doi: 10.1016/j.bbrc.2003.10.080.
Myostatin is a new member of the transforming growth factor-beta (TGFbeta) superfamily and functions as a negative regulator of skeletal muscle growth. Herein, we report the identification of a myostatin-associated protein hSGT (human small glutamine-rich tetratricopeptide repeat-containing protein) by using a yeast two-hybrid system. The physical interaction between hSGT and myostatin was further confirmed by pull-down and co-immunoprecipitation experiments. To identify regions involved in the interaction between hSGT and myostatin, we constructed various deletion mutants of hSGT and myostatin, respectively, and examined their interactions in yeast cells. Our results showed that the N-terminal signal peptide of myostatin is essential for its association with hSGT and the C-terminal region of hSGT containing the third TPR motif was indispensable for its interaction with myostatin. Recent studies indicate that hSGT probably functions as a molecular chaperone involved in protein folding and processing. These findings suggest that hSGT may play a role in the regulation of myostatin secretion and activation.
肌肉生长抑制素是转化生长因子-β（TGFβ）超家族的新成员，作为骨骼肌生长的负调节因子发挥作用。在此，我们报告了通过酵母双杂交系统鉴定出一种与肌肉生长抑制素相关的蛋白hSGT（富含小谷氨酰胺的四肽重复序列的人类蛋白）。hSGT与肌肉生长抑制素之间的物理相互作用通过下拉实验和共免疫沉淀实验得到进一步证实。为了确定hSGT与肌肉生长抑制素相互作用所涉及的区域，我们分别构建了hSGT和肌肉生长抑制素的各种缺失突变体，并在酵母细胞中检测它们的相互作用。我们的结果表明，肌肉生长抑制素的N端信号肽对于其与hSGT的结合至关重要，而hSGT含有第三个TPR基序的C端区域对于其与肌肉生长抑制素的相互作用是不可或缺的。最近的研究表明，hSGT可能作为一种分子伴侣参与蛋白质折叠和加工。这些发现表明，hSGT可能在肌肉生长抑制素的分泌和激活调节中发挥作用。
