The inhibition of degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by sterol regulatory element binding protein cleavage-activating protein requires four phenylalanine residues in span 6 of HMG-CoA reductase transmembrane domain

2003 ◽  
Vol 414 (2) ◽  
pp. 232-243 ◽  
Author(s):  
Liwen Xu ◽  
Robert D Simoni
Keyword(s):  
Coenzyme A ◽  
Transmembrane Domain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Protein Cleavage ◽  
Hmg Coa Reductase ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Coa Reductase

scholarly journals Sterol Regulatory Element Binding Protein 1a Regulates Hepatic Fatty Acid Partitioning by Activating Acetyl Coenzyme A Carboxylase 2

2009 ◽  
Vol 29 (17) ◽  
pp. 4864-4872 ◽  
Author(s):  
Seung-Soon Im ◽  
Linda E. Hammond ◽  
Leyla Yousef ◽  
Cherryl Nugas-Selby ◽  
Dong-Ju Shin ◽  
...  
Keyword(s):  
Insertional Mutagenesis ◽  
Coenzyme A ◽  
Binding Protein ◽  
Regulatory Element ◽  
Fatty Acyl ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Microarray Expression

ABSTRACT We generated a line of mice in which sterol regulatory element binding protein 1a (SREBP-1a) was specifically inactivated by insertional mutagenesis. Homozygous mutant mice were completely viable despite expressing SREBP-1a mRNA below 5% of normal, and there were minimal effects on expression of either SREBP-1c or -2. Microarray expression studies in liver, where SREBP-1a mRNA is 1/10 the level of the highly similar SREBP-1c, demonstrated that only a few genes were affected. The only downregulated genes directly linked to lipid metabolism were Srebf1 (which encodes SREBP-1) and Acacb (which encodes acetyl coenzyme A [acetyl-CoA] carboxylase 2 [ACC2], a critical regulator of fatty acyl-CoA partitioning between cytosol and mitochondria). ACC2 regulation is particularly important during food restriction. Similar to Acacb knockout mice, SREBP-1a-deficient mice have lower hepatic triglycerides and higher serum ketones during fasting than wild-type mice. SREBP-1a and -1c have identical DNA binding and dimerization domains; thus, the failure of the more abundant SREBP-1c to substitute for activating hepatic ACC2 must relate to more efficient recruitment of transcriptional coactivators to the more potent SREBP-1a activation domain. Our chromatin immunoprecipitation results support this hypothesis.

Inhibition of sterol regulatory element-binding protein cleavage by the prodomain of human SKI-1 protease

2000 ◽  
Vol 151 (1) ◽  
pp. 287
Author(s):  
R. Laaksonen ◽  
C. Lefebvre ◽  
J. Lavigne ◽  
E. Priceputu ◽  
L. Bernier ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Protein Cleavage ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: role of sterol regulatory element binding protein 2

2007 ◽  
Vol 292 (1) ◽  
pp. G369-G376 ◽  
Author(s):  
Waddah A. Alrefai ◽  
Fadi Annaba ◽  
Zaheer Sarwar ◽  
Alka Dwivedi ◽  
Seema Saksena ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Absorption ◽  
Cholesterol Depletion ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Niemann Pick ◽  
Coa Reductase

Niemann-Pick C1-like 1 (NPC1L1) is an essential intestinal component of cholesterol absorption. However, little is known about the molecular regulation of intestinal NPC1L1 expression and promoter activity. We demonstrated that human NPC1L1 mRNA expression was significantly decreased by 25-hydroxycholesterol but increased in response to cellular cholesterol depletion achieved by incubation with Mevinolin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase) in human intestinal Caco-2 cells. We also showed that a −1741/+56 fragment of the NPC1L1 gene demonstrated high promoter activity in Caco-2 cells that was reduced by 25-hydroxycholesterol and stimulated by cholesterol depletion. Interestingly, we showed that the NPC1L1 promoter is remarkably transactivated by the overexpression of sterol regulatory element (SRE) binding protein (SREBP)-2, suggesting its involvement in the sterol-induced alteration in NPC1L1 promoter activity. Finally, we identified two putative SREs in the human NPC1L1 promoter and established their essential roles in mediating the effects of cholesterol on promoter activity. Our study demonstrated the modulation of human NPC1L1 expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism.

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