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Endoplasmic reticulum (ER)-associated degradation (ERAD) is required for ubiquitin-mediated destruction of numerous proteins. ERAD occurs by processes on both sides of the ER membrane, including lumenal substrate scanning and cytosolic destruction by the proteasome. The ER resident membrane proteins Hrd1p and Hrd3p play central roles in ERAD. We show that(More)
The internal environment of the ER is regulated to accommodate essential cellular processes, yet our understanding of this regulation remains incomplete. Cod1p/Spf1p belongs to the widely conserved, uncharacterized type V branch of P-type ATPases, a large family of ion pumps. Our previous work suggested Cod1p may function in the ER. Consistent with this(More)
The integral ER membrane protein HMG-CoA reductase (HMGR) is a key enzyme of the mevalonate pathway from which sterols and other essential molecules are produced. HMGR degradation occurs in the ER and is regulated by mevalonate-derived signals. Little is known about the mechanisms responsible for regulating HMGR degradation. The yeast Hmg2p isozyme of HMGR(More)
The degradation rate of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-R), a key enzyme of the mevalonate pathway, is regulated through a feedback mechanism by the mevalonate pathway. To discover the intrinsic determinants involved in the regulated degradation of the yeast HMG-R isozyme Hmg2p, we replaced small regions of the Hmg2p transmembrane domain with(More)
INSIGs are proteins that underlie sterol regulation of the mammalian proteins SCAP (SREBP cleavage activating protein) and HMG-CoA reductase (HMGR). The INSIGs perform distinct tasks in the regulation of these effectors: they promote ER retention of SCAP, but ubiquitin-mediated degradation of HMGR. Two questions that arise from the discovery and study of(More)