Access Restriction

Source CiteSeerX
Content type Text
File Format PDF
Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Subject Keyword Polytopic Protein ♦ Recruit Proteasomes Insig-1 Extraction Frommembranes ♦ Endoplasmic Reticulum-associated Degradation ♦ Negative Regulator ♦ Polytopic Erprotein ♦ Single Amino Acid Substitution ♦ Cholesterol Synthesis ♦ Sterol-regulated Manner ♦ Functional Homologue ♦ Sterol Accumulate ♦ Mutant Insig-2 ♦ Accelerated Degradation ♦ Er-associated Degradation ♦ Type Insig-1
Abstract Polytopicmembraneproteins subjected to endoplasmic retic-ulum (ER)-associated degradation are extracted from mem-branes and targeted to proteasomes for destruction. The extrac-tionmechanism is poorly understood.One polytopic ERprotein subjected to ER-associated degradation is Insig-1, a negative regulator of cholesterol synthesis. Insig-1 is rapidly degraded by proteasomes when cells are depleted of cholesterol, and its deg-radation is inhibited when sterols accumulate in cells. Insig-2, a functional homologue of Insig-1, is degraded slowly, and its degradation is not regulated by sterols. Here, we report that a single amino acid substitution in Insig-2, Insig-2(L210A), causes Insig-2 to be degraded in an accelerated and sterol-regulated manner similar to Insig-1. In seeking an explanation for the accelerated degradation, we found that proteasomes bind to wild type Insig-1 and mutant Insig-2(L210A) but not to wild
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study