酸性鞘磷脂酶衍生的神经酰胺靶向组织蛋白酶D。
Cathepsin D targeted by acid sphingomyelinase-derived ceramide.
作者信息
Heinrich M, Wickel M, Schneider-Brachert W, Sandberg C, Gahr J, Schwandner R, Weber T, Saftig P, Peters C, Brunner J, Krönke M, Schütze S
机构信息
Institute of Immunology, University of Kiel, Kiel, Germany.
出版信息
EMBO J. 1999 Oct 1;18(19):5252-63. doi: 10.1093/emboj/18.19.5252.
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.
神经酰胺已被公认为是多种细胞因子、生长因子及其他刺激因素（如CD95、化疗药物和应激因素）共同的细胞内第二信使。为了解神经酰胺在细胞凋亡及其他细胞反应过程中的作用，明确神经酰胺作用的直接靶点至关重要。在本文中，我们表明神经酰胺能特异性结合并激活内体酸性天冬氨酸蛋白酶组织蛋白酶D。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前体蛋白发生自催化蛋白水解，形成具有酶活性的48/32 kDa组织蛋白酶D同工型。酸性鞘磷脂酶（A-SMase）缺陷细胞的组织蛋白酶D活性降低，转染A-SMase cDNA可使其恢复。我们的研究结果确定组织蛋白酶D是首个与A-SMase共定位并可能介导其下游信号效应的内体神经酰胺靶点。
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