蛋白酶体抑制剂对胰岛素原受体成熟的影响：一个解剖学悖论。

Effects of proteasomal inhibitors on the maturation of the insulin proreceptor: an anatomical paradox.

作者信息

Tomic-Carruthers N, Gorden P

机构信息

Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.

出版信息

Biochem Biophys Res Commun. 1998 Mar 27;244(3):728-31. doi: 10.1006/bbrc.1998.8333.

DOI:10.1006/bbrc.1998.8333

PMID:9535733

Abstract

Inhibitors of proteasomal functions Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and Carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-alanyl-L-leucinal (PSI) were found to inhibit the conversion of the Insulin proreceptor to its mature alpha and beta subunits. By contrast no effect of these inhibitors was found on 125-I insulin binding, internalization and degradation. Since the insulin proreceptor is an integral membrane protein that is compartmentally separated from the cytoplasmic 26S proteasome, the inhibition of the normal biosynthetic processing of the insulin proreceptor presents an anatomical paradox.

摘要

蛋白酶体功能抑制剂苄氧羰基-L-亮氨酰-L-亮氨酰-L-亮氨酸醛（MG132）和苄氧羰基-L-异亮氨酰-γ-叔丁基-L-丙氨酰-L-亮氨酸醛（PSI）被发现可抑制胰岛素前体受体向其成熟的α和β亚基的转化。相比之下，未发现这些抑制剂对¹²⁵-I胰岛素结合、内化和降解有影响。由于胰岛素前体受体是一种整合膜蛋白，与细胞质中的26S蛋白酶体在区域上是分开的，因此胰岛素前体受体正常生物合成加工过程的抑制呈现出一种解剖学上的矛盾。