Lipid-regulated degradation of HMG-CoA reductase and Insig-1 through distinct mechanisms in insect cells
نویسندگان
چکیده
منابع مشابه
Lipid-regulated degradation of HMG-CoA reductase and Insig-1 through distinct mechanisms in insect cells
In mammalian cells, levels of the integral membrane proteins 3-hydroxy-3-methylglutaryl-CoA reductase and Insig-1 are controlled by lipid-regulated endoplasmic reticulum-associated degradation (ERAD). The ERAD of reductase slows a rate-limiting step in cholesterol synthesis and results from sterol-induced binding of its membrane domain to Insig-1 and the highly related Insig-2 protein. Insig bi...
متن کاملDifferential regulation of HMG-CoA reductase and Insig-1 by enzymes of the ubiquitin-proteasome system
The endoplasmic reticulum (ER)-resident enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase catalyzes the rate-limiting step in sterol production and is the therapeutic target of statins. Understanding HMG-CoA reductase regulation has tremendous implications for atherosclerosis. HMG-CoA reductase levels are regulated in response to sterols both transcriptionally, through a complex regulat...
متن کاملDislocation of HMG-CoA reductase and Insig-1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation.
The endoplasmic reticulum (ER) glycoprotein HMG-CoA reductase (HMGR) catalyzes the rate-limiting step in sterols biosynthesis. Mammalian HMGR is ubiquitinated and degraded by the proteasome when sterols accumulate in cells, representing the best example for metabolically controlled ER-associated degradation (ERAD). This regulated degradation involves the short-lived ER protein Insig-1. Here, we...
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Numerous integral membrane proteins are degraded in the mammalian ER. HMG-CoA reductase (HMG-R), a key enzyme in the mevalonate pathway by which isoprenoids and sterols are synthesized, is one substrate of ER degradation. The degradation of HMG-R is modulated by feedback signals from the mevalonate pathway. We investigated the role of regulated degradation of the two isozymes of HMG-R, Hmg1p an...
متن کاملInsig regulates HMG-CoA reductase by controlling enzyme phosphorylation in fission yeast.
Insig functions as a central regulator of cellular cholesterol homeostasis by controlling activity of HMG-CoA reductase (HMGR) in cholesterol synthesis. Insig both accelerates the degradation of HMGR and suppresses HMGR transcription through the SREBP-Scap pathway. The fission yeast Schizosaccharomyces pombe encodes homologs of Insig, HMGR, SREBP, and Scap, called ins1(+), hmg1(+), sre1(+), and...
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ژورنال
عنوان ژورنال: Journal of Lipid Research
سال: 2013
ISSN: 0022-2275
DOI: 10.1194/jlr.m033639