1996
DOI: 10.1074/jbc.271.21.12247
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A Direct Role for Sterol Regulatory Element Binding Protein in Activation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Gene

Abstract: In earlier studies the DNA site required for sterol regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase was shown to be distinct from the classic sterol regulatory element (SRE-1) of the low density lipoprotein receptor gene (Osborne, The SREBP proteins are special members of the basichelix-loop-helix-zipper (bHLHZip) family of DNA binding proteins since they bind the classic palindromic Ebox site as well as the direct repeat SRE-1 element. The SREBP binding sites in both the reductase and those rece… Show more

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Cited by 214 publications
(153 citation statements)
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“…The nucleotide sequence in this upstream flanking region is unremarkable, except for a short GC-rich sequence that is partially conserved in both CWP1 and CWP2. This sequence has been hypothesized to be a sterol regulatory element (Lujan et al, 1997), involved in cholesterol-sensitive transcription regulation (Goldstein and Brown, 1990;Vallett et al, 1996;Bist et A.B. Hehl et al al., 1997).…”
Section: Discussionmentioning
confidence: 99%
“…The nucleotide sequence in this upstream flanking region is unremarkable, except for a short GC-rich sequence that is partially conserved in both CWP1 and CWP2. This sequence has been hypothesized to be a sterol regulatory element (Lujan et al, 1997), involved in cholesterol-sensitive transcription regulation (Goldstein and Brown, 1990;Vallett et al, 1996;Bist et A.B. Hehl et al al., 1997).…”
Section: Discussionmentioning
confidence: 99%
“…The reaction was stopped by heating the tubes for 3 min at 98 8C. 10 mL of each sample was applied as a band on a TLC plate and the plate was developed in methanol:0.6% NaCl:NH 4 Lamellar-to-hexagonal phase transition 31 P-NMR was used to measure the effects of sterols on the L a ± H II -transition in multilamellar liposomes prepared from bovine brain phospholipids. The lipids (phosphatidylcholine, phosphatidylethanolamine and one of the sterols at a 2 : 2 : 1 mol ratio) were pipetted into a glass tube, into which 5 mol percentage dioleoylglycerol (DOG) also was added [21].…”
Section: Metabolic Labelling Of Cell Phosphatidylcholinementioning
confidence: 99%
“…In cells depleted of sterols, a two-step proteolytic process releases the N-terminal segment of the SREBP. This polypeptide then enters the nucleus and activates transcription of genes encoding the LDL receptor and several enzymes in the cholesterol biosynthetic pathway, including HMG-CoA reductase [4]. The first proteolytic cleavage is regulated by a membrane-bound SREBP cleavage activating protein (SCAP) [5].…”
mentioning
confidence: 99%
“…Similar to other proteins of the MVA pathway (Horton et al, 2002), HMGR is controlled also at the transcriptional level by the sterol regulatory element-binding protein (SREBP)-2, which binds to the promoter of the HMGR gene and activates transcription when demands for MVA-derived products increase (Osborne et al, 1985;Vallett et al, 1996). Like its closely related SREBP-1a and SREBP-1c factors, SREBP-2 is synthesized as a large endoplasmic reticulum (ER)-bound precursor whose transcription activation domain must be released from the membrane to function in the nucleus.…”
Section: Introductionmentioning
confidence: 99%
“…This enzyme catalyzes the rate-limiting step in the mevalonate (MVA) pathway in which essential sterols and nonsterol isoprenoids are synthesized (Goldstein and Brown, 1990). In cells deprived of sterols and/or MVA-derived isoprenoids, HMGR is a fairly stable protein that turns over with a half-life of 10 -14 h. Conversely, in cells replenished with MVA pathway products, HMGR degradation is accelerated severalfold and its half-life drops to 1-4 h (Faust et al, 1982;Edwards et al, 1983;Sinensky and Logel, 1983), reflecting one of the highly regulated processes that prevent accumulation of these metabolites to toxic levels.Similar to other proteins of the MVA pathway (Horton et al, 2002), HMGR is controlled also at the transcriptional level by the sterol regulatory element-binding protein (SREBP)-2, which binds to the promoter of the HMGR gene and activates transcription when demands for MVA-derived products increase (Osborne et al, 1985;Vallett et al, 1996). Like its closely related SREBP-1a and SREBP-1c factors, SREBP-2 is synthesized as a large endoplasmic reticulum (ER)-bound precursor whose transcription activation domain must be released from the membrane to function in the nucleus.…”
mentioning
confidence: 99%