SYNTHESIS AND FUNCTION OF A TRANSFORMATION-DEPENDENT SECRETED LYSOSOMAL PROTEASE

转化依赖性分泌型溶酶体蛋白酶的合成和功能

• 批准号: 3796485
• 负责人: M M GOTTESMAN
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3796485
• 关键词: RNA splicing; animal tissue; antigen presentation; carcinoma; cell transformation; chemical carcinogen; chromatography; complementary DNA; electrophoresis; endoplasmic reticulum; enzyme activity; enzyme biosynthesis; enzyme induction /repression; enzyme structure; fibroblasts; gene deletion mutation; genetic manipulation; genetic promoter element; genetic regulation; genetic transcription; human genetic material tag; human tissue; in situ hybridization; laboratory mouse; lung neoplasms; lysosomes; messenger RNA; molecular cloning; neoplasm /cancer genetics; neoplastic cell; neoplastic transformation; nucleic acid probes; nucleic acid sequence; oncoproteins; peptidases; phorbols; platelet derived growth factor; protein biosynthesis; protein folding; protein metabolism; secretion; secretory protein; testis neoplasms; tissue /cell culture; transforming growth factors; zymogens

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.

组织蛋白酶原L（也称为MEP，主要排泄蛋白）是一种蛋白酶。 溶酶体蛋白酶，其由蛋白酶合成并大量分泌， 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是一种半胱氨酸酸性蛋白酶， 广泛的底物特异性，包括许多细胞外基质 印刷受体. 为了了解组织蛋白酶L的调节模式，我们 分离出小鼠和人类的基因并研究它们的上游， 启动子区。 小鼠启动子具有位于启动子5'和3'端的元件。 影响肿瘤调控的转录起始位点 启动子，TPA。 人类基因，定位于9号染色体，似乎 具有两个不同的启动子，其决定两种转录物的表达 在大多数人体组织中。 一个全长人类基因的缺失分析 在培养的小鼠细胞中表达的组织蛋白酶原L cDNA揭示了许多 参与亚细胞定位的蛋白质的特征， 功能 蛋白质氨基末端的序列 参与蛋白质折叠，它们的缺失导致捕获 在内质网中的表达。 氨基酸残基 组织蛋白酶L羧基末端影响其被 秘密的