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

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.