LYSOSOMAL PHYSIOLOGY & PROTEIN DEGRADATION IN CYSTINOSIS

不同营养条件下细胞蛋白分解的调控机制 情况仍然知之甚少，尽管蛋白质之间的平衡 合成和降解似乎是一项基本要求 活细胞在整个细胞周期中提供动态平衡。数不胜数 几种猪链球菌溶酶体和非溶酶体蛋白分解的研究 蛋白质产生了相互矛盾的结果。我们建议调查 利用细胞的独特特性进行细胞蛋白分解 人类突变，胱氨酸病，导致这些 一旦溶酶体形成，细胞就将胱氨酸运出溶酶体 在那里，含有半胱氨酸的蛋白质被降解。我们会做好准备 ~(35)S-半胱氨酸代谢标记的纯化蛋白 二硫键并研究生成的溶酶体35S-半胱氨酸 将其导入人膀胱癌成纤维细胞后的蓄积 细胞通过内吞、吞饮或微量注射。结果是 应加强对血吸虫病的基因定位和调控机制的认识 细胞蛋白分解。

The regulatory mechanisms for cellular proteolysis under varied nutritional conditions remain poorly understood, although a balance between protein synthesis and degradation would appear to be a fundamental requirement of living cells to provide homeostasis throughout the cell cycle. Numerous studies of the lysosomal and nonlysosomal proteolysis of a variety of proteins have produced conflicting results. We propose to investigate cellular proteolysis by taking advantage of the unique characteristic of the human mutation, cystinosis, which results in the inability of these cells to transport cystine out of the lysosome once it has been formed there from the degradation of cystine-containing proteins. We will prepare purified proteins metabolically labelled with 35S-cystine in their disulfide moieties and study the resultant lysosomal 35S-cystine accumulation in cystinotic fibroblasts produced after introducing them to the cell via endocytosis, pinocytosis or microinjection. The results should enhance our understanding of the loci and regulatory mechanisms of cellular proteolysis.