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Protein-protein interaction studies in the Saccharomyces cerevisiae ergosterol biosynthetic pathway suggest that enzymes in this pathway may act as an integrated multienzyme complex. The yeast sterol 3-ketoreductase (Erg27p) required for C-4 demethylation of sterols has previously been shown to also be required for the function of the upstream oxidosqualene(More)
Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors (PERK, ATF6, and IRE1) implement the UPR.(More)
Different environmental stresses induce the phosphorylation of eIF2 (eIF2∼P), repressing global protein synthesis coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of genes involved in metabolism and nutrient uptake, antioxidation, and regulation of apoptosis. Because ATF4 is a common downstream target that integrates(More)
Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control(More)
In Saccharomyces cerevisiae and Candida albicans, two enzymes of the ergosterol biosynthetic pathway, oxidosqualene cyclase (Erg7p) and 3-keto reductase (Erg27p) interact such that loss of the 3-keto reductase also results in a concomitant loss of activity of the upstream oxidosqualene cyclase. This interaction wherein Erg27p has a stabilizing effect on(More)
Endoplasmic reticulum (ER) stress induces a program of translational and transcriptional regulation, designated the unfolded protein response (UPR), that collectively remedies stress damage and restores ER homeostasis. The protein kinase PERK facilitates the translational control arm of the UPR by phosphorylation of eIF2, a translation initiation factor(More)
In mammals and yeasts, oxidosqualene cyclase (OSC) catalyzes the formation of lanosterol, the first cyclic intermediate in sterol biosynthesis. We used a murine myeloma cell line (NS0), deficient in the 17β-hydroxysteroid dehydrogenase type 7 (HSD17B7), as a model to study the potential interaction of the HSD17B7 with the OSC in mammals. HSD17B7 is the(More)
This study examined the feasibility of using quantitation to augment interpretation of florbetapir PET amyloid imaging. A total of 80 physician readers were trained on quantitation of florbetapir PET images and the principles for using quantitation to augment a visual read. On day 1, the readers completed a visual read of 96 scans (46 autopsy-verified and(More)
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