Relatedness of human interleukin-1beta convertase gene to a C. elegans cell death gene, inhibitory portions of these genes and uses therefor
申请人:——
公开号:US20020136714A1
公开(公告)日:2002-09-26
Described herein is the discovery that human interleukin-1&bgr; convertase (ICE) is structurally similar to the protein encoded by the
C. elegans
cell death gene, ced-3. Comparative and mutational analyses of the two proteins, together with previous observations, suggest that the Ced-3 protein may be a cysteine protease like ICE and that ICE may be a human equivalent of the nematode cell death gene. Another mammalian protein, the murine NEDD-2 protein, was also found to be similar to Ced-3. The NEDD-2 gene is implicated in the development of the murine central nervous system. On the basis of these findings, novel drugs for enhancing or inhibiting the activity of ICE, ced-3, or related genes are provided. Such drugs may be useful for treating inflammatory diseases and/or diseases characterized by cell deaths, as well as cancers, autoimmune disorders, infections, and hair growth and hair loss. Furthermore, such drugs may be useful for controlling pests, parasites and genetically engineered organisms. Furthermore, novel inhibitors of the activity of ced-3, ICE and related genes are described which comprise portions of the genes or their encoded products.
本文描述了人类白细胞介素-1&bgr; 转换酶(ICE)在结构上类似于由
细胞死亡基因
细胞死亡基因 ced-3 所编码的蛋白质相似。对这两种蛋白质的比较分析和突变分析,以及以前的观察结果表明,Ced-3 蛋白可能是一种类似于 ICE 的半胱氨酸蛋白酶,而 ICE 可能是线虫细胞死亡基因在人类的等同物。研究还发现另一种哺乳动物蛋白--鼠类 NEDD-2 蛋白与 Ced-3 相似。NEDD-2 基因与小鼠中枢神经系统的发育有关。根据这些发现,提供了增强或抑制 ICE、ced-3 或相关基因活性的新型药物。这类药物可用于治疗炎症性疾病和/或以细胞死亡为特征的疾病,以及癌症、自身免疫性疾病、感染、生发和脱发。此外,这类药物还可用于控制害虫、寄生虫和基因工程生物。此外,还描述了 ced-3、ICE 和相关基因活性的新型抑制剂,其中包括这些基因或其编码产物的一部分。