糖皮质激素调节元件结合蛋白1通过与半胱天冬酶募集结构域的相互作用对前半胱天冬酶-2进行调节。

Regulation of procaspase-2 by glucocorticoid modulatory element-binding protein 1 through the interaction with caspase recruitment domain.

作者信息

Tsuruma Kazuhiro, Nakagawa Tadashi, Shirakura Hiromi, Hayashi Naoko, Uehara Takashi, Nomura Yasuyuki

机构信息

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Sapporo 060-0812, Japan.

出版信息

Biochem Biophys Res Commun. 2004 Dec 24;325(4):1246-51. doi: 10.1016/j.bbrc.2004.10.145.

DOI:10.1016/j.bbrc.2004.10.145

PMID:15555560

Abstract

Caspases are the primary executioners of apoptosis. Although procaspases believe to exist as inactive forms in cells, the detailed regulatory system remains unclear. Here we show that glucocorticoid modulatory element-binding protein 1 (GMEB1) is capable of binding to the prodomain of caspase-2. We found that this molecule inhibits the autoproteolytic activation of procaspase-2 by oligomerization on a chemical compound-dependent system. These findings indicated that GMEB1 might be an endogenous inhibitory protein that selectively interacts with prodomain of caspase-2 to disrupt the autoactivation.

摘要

半胱天冬酶是细胞凋亡的主要执行者。尽管人们认为半胱天冬酶原在细胞中以无活性形式存在，但其详细的调节系统仍不清楚。在此，我们表明糖皮质激素调节元件结合蛋白1（GMEB1）能够与半胱天冬酶-2的前结构域结合。我们发现，该分子在一种化合物依赖性系统上通过寡聚化抑制半胱天冬酶原-2的自蛋白水解激活。这些发现表明，GMEB1可能是一种内源性抑制蛋白，它选择性地与半胱天冬酶-2的前结构域相互作用以破坏自激活。