TY - JOUR
T1 - Regulation of HMG-CoA reductase in mammals and yeast
AU - Burg, John S.
AU - Espenshade, Peter J.
N1 - Funding Information:
We extend a sincere apology to those whose work was not discussed or cited in this review due to limitations in space and scope. This work was supported by a grant from the National Institutes of Health ( HL-077588 ). P.J.E. is an Established Investigator of the American Heart Association.
PY - 2011/10
Y1 - 2011/10
N2 - HMG-CoA reductase (HMGR), a highly conserved, membrane-bound enzyme, catalyzes a rate-limiting step in sterol and isoprenoid biosynthesis and is the primary target of hypocholesterolemic drug therapy. HMGR activity is tightly regulated to ensure maintenance of lipid homeostasis, disruption of which is a major cause of human morbidity and mortality. HMGR regulation takes place at the levels of transcription, translation, post-translational modification and degradation. In this review, we discuss regulation of mammalian, Saccharomyces cerevisiae and Schizosaccharomyces pombe HMGR and highlight recent advances in the field. We find that the general features of HMGR regulation, including a requirement for the HMGR-binding protein Insig, are remarkably conserved between mammals and ascomycetous fungi, including S. cerevisiae and S. pombe. However the specific details by which this regulation occurs differ in surprising ways, revealing the broad evolutionary themes underlying both HMGR regulation and Insig function.
AB - HMG-CoA reductase (HMGR), a highly conserved, membrane-bound enzyme, catalyzes a rate-limiting step in sterol and isoprenoid biosynthesis and is the primary target of hypocholesterolemic drug therapy. HMGR activity is tightly regulated to ensure maintenance of lipid homeostasis, disruption of which is a major cause of human morbidity and mortality. HMGR regulation takes place at the levels of transcription, translation, post-translational modification and degradation. In this review, we discuss regulation of mammalian, Saccharomyces cerevisiae and Schizosaccharomyces pombe HMGR and highlight recent advances in the field. We find that the general features of HMGR regulation, including a requirement for the HMGR-binding protein Insig, are remarkably conserved between mammals and ascomycetous fungi, including S. cerevisiae and S. pombe. However the specific details by which this regulation occurs differ in surprising ways, revealing the broad evolutionary themes underlying both HMGR regulation and Insig function.
KW - AMPK
KW - ERAD
KW - HMG-CoA reductase
KW - HRD
KW - Insig
KW - Sterol
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U2 - 10.1016/j.plipres.2011.07.002
DO - 10.1016/j.plipres.2011.07.002
M3 - Review article
C2 - 21801748
AN - SCOPUS:79961118496
SN - 0163-7827
VL - 50
SP - 403
EP - 410
JO - Progress in Lipid Research
JF - Progress in Lipid Research
IS - 4
ER -