Cathepsin D targeted by acid sphingomyelinase-derived ceramide
Cathepsin D targeted by acid sphingomyelinase-derived ceramide
复制标题
DOI：
10.1093/emboj/18.19.5252
复制
发表时间：
1999-10-01
期刊：
影响因子：
11.4
通讯作者：
Schütze, S
中科院分区：
文献类型：
--
作者：
Heinrich, M;Wickel, M;Schütze, S
神经酰胺被认为是多种细胞因子、生长因子和其他刺激物（如CD 95、化疗药物和应激因子）的共同细胞内第二信使。为了了解神经酰胺在细胞凋亡和其他细胞反应中的作用，描述神经酰胺作用的直接靶点至关重要。神经酰胺与组织蛋白酶D的直接相互作用导致52 kDa的组织蛋白酶D前体蛋白酶原自催化水解形成具有酶活性的组织蛋白酶D的48/32 kDa异构体。酸性鞘磷脂酶（A-SMase）缺陷的细胞表现出降低的组织蛋白酶D活性，这可以通过转染A-SMase cDNA来重建。我们的研究结果确定组织蛋白酶D是第一个与A-SMase共定位并可能介导A-SMase下游信号传导作用的内体神经酰胺靶点。
Ceramide has been recognized as a common intracellular second messenger for various cytokines, growth factors and other stimuli, such as CD95, chemotherapeutic drugs and stress factors. To understand the role of ceramide during apoptosis and other cellular responses, it is critically important to characterize direct targets of ceramide action. In this paper, we show that ceramide specifically binds to and activates the endosomal acidic aspartate protease cathepsin D, Direct interaction of ceramide with cathepsin D results in autocatalytic proteolysis of the 52 kDa pre-pro cathepsin D to form the enzymatically active 48/32 kDa isoforms of cathepsin D. Acid sphingomyelinase (A-SMase)-deficient cells show decreased cathepsin D activity, which could be reconstituted by transfection with A-SMase cDNA, The results of our study identify cathepsin D as the first endosomal ceramide target that colocalizes with and may mediate downstream signaling effects of A-SMase.