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.
Tomic-Carruthers
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Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
Gorden
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P
D016475:3T3 Cells; D000818:Animals; D002451:Cell Compartmentation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009097:Multienzyme Complexes; D009842:Oligopeptides; D011498:Protein Precursors; D011994:Recombinant Proteins; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; C051512:insulin proreceptor; D011972:Receptor, Insulin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde