SYNTHESIS AND FUNCTION OF A TRANSFORMATION-DEPENDENT SECRETED LYSOSOMAL PROTEASE

Procathepsin L(又称MEP，主要排泄蛋白)是一种 大量合成和分泌的溶酶体蛋白酶。 恶性转化的小鼠和人类细胞以及正常细胞 肾脏和肝脏。组织蛋白酶L是一种半胱氨酸蛋白酶，具有 广泛的底物专一性，包括许多细胞外基质 底物。为了了解组织蛋白L的调节模式，我们有 分离了老鼠和人类的基因并研究了它们的上游， 启动子区域。小鼠启动子含有5‘和3’元件。 影响肿瘤调控的转录起始位置 启动子，TPA。映射到9号染色体的人类基因似乎 有两个不同的启动子，它们决定了两个转录本的表达 在大多数人体组织中。一个全长人类的缺失分析 在培养的小鼠细胞中表达的L原蛋白显示了许多 参与亚细胞定位的蛋白质的特征和 功能。出现蛋白质的氨基末端部分的序列 参与蛋白质折叠和它们的缺失导致捕获 L酶原在内质网中的表达。氨基酸残基在 组织蛋白L的羧基末端影响其结合能力 秘而不宣。

Procathepsin L (also known as MEP, for major excreted protein) is a lysosomal protease which is synthesized and secreted in large amounts by malignantly transformed mouse and human cells, as well as by normal cells of the kidney and liver. Cathepsin L is a cysteine acid protease with a broad substrate specificity which includes many extracellular matrix substrates. To understand the mode of regulation of cathepsin L, we have isolated both the mouse and human genes and studied their upstream, promoter regions. The mouse promoter has elements both 5' and 3' to the start site of transcription which affect regulation by the tumor promoter, TPA. The human gene, which maps to chromosome 9, appears to have two distinct promoters which determine expression of two transcripts in most human tissues. A deletion analysis of a full-length human procathepsin L cDNA expressed in cultured mouse cells has revealed many features of the protein involved in subcellular localization and function. Sequences in the amino terminal section of the protein appear to be involved in protein folding and their deletion results in trapping of procathepsin L in the endoplasmic reticulum. Amino acid residues at the carboxy terminal end of cathepsin L affect its ability to be secreted.