Quality control of inner nuclear membrane proteins by the Asi complex

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Science  18 Sep 2014:
DOI: 10.1126/science.1255638

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Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a quality-control system called ER-associated protein degradation (ERAD). However, how misfolded proteins in the inner nuclear membrane (INM), a specialized ER subdomain, are degraded is not known. Here, a quantitative proteomics approach revealed an ERAD branch required for INM protein quality control in yeast. This branch involved the integral membrane proteins Asi1, Asi2, and Asi3, which assembled into an Asi complex. Besides INM misfolded proteins, the Asi complex promoted the degradation of functional regulators of sterol biosynthesis. Asi-mediated ERAD was required for ER homeostasis, which suggests that spatial segregation of protein quality-control systems contributes to ER function.

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