Hur Eun-Hye, Hur Wonhee, Choi Ju-Youn, Kim In-Kyung, Kim Ho-Youn, Yoon Seung Kew, Rhim Hyangshuk
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Biochem Biophys Res Commun. 2004 Dec 3;325(1):59-67. doi: 10.1016/j.bbrc.2004.09.215.
Recent studies provide evidence that Sox4 is involved in regulating apoptosis as well as tumorigenesis of various human cancers; however, its role in the apoptotic machinery is not fully understood. Here we describe that the central domain containing glycine-rich region in Sox4, named CD, is a pivotal pro-apoptotic domain to induce apoptotic cell death. Deletion of the DNA-binding domain or trans-activation domain in Sox4 did not significantly affect pro-apoptotic activity, whereas transient transfection of the high mobility group box or the serine-rich region abrogated the apoptotic activity. Moreover, overexpression of the CD construct (aa 166-342) revealed the apoptotic activity comparable to that of wild-type Sox4, approximately 60% of cell death. Our data suggest that the apoptotic activity of Sox4 can be dissociated from its transcriptional trans-activation and is mediated through its CD.
近期研究表明，Sox4参与调控多种人类癌症的细胞凋亡及肿瘤发生；然而，其在凋亡机制中的作用尚未完全明确。在此我们描述，Sox4中包含富含甘氨酸区域的中央结构域（称为CD）是诱导凋亡细胞死亡的关键促凋亡结构域。Sox4中DNA结合结构域或反式激活结构域的缺失对促凋亡活性无显著影响，而高迁移率族框或富含丝氨酸区域的瞬时转染则消除了凋亡活性。此外，CD构建体（氨基酸166 - 342）的过表达显示出与野生型Sox4相当的凋亡活性，约60%的细胞死亡。我们的数据表明，Sox4的凋亡活性可与其转录反式激活作用分离，并通过其CD结构域介导。
