Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the biosynthesis of fatty acids, is induced in the presence of high glucose levels. The ACC gene contains two promoters: promoter I (PI) expression is inducible under lipogenic conditions, while promoter II (PII) expression, even though constitutively expressed in all tissues, is also controlled under various physiological conditions. Examination of the expression pattern of a series of deletion constructs of PII showed that the region from -340 to -249 was essential for ACC induction. In addition, by electrophoretic mobility shift assays, supershift assays, and DNase I footprinting studies, we have detected the binding of the transcription factor Sp1 at the two GC-rich sequences located within the -340 to -249 region of promoter II. Mutations at the GC-rich sequences prevented binding of Sp1, and the induction of the PII promoter was no longer observed. Cotransfection studies, in Drosophila Schneider SL2 cells, with the Sp1 expression vector and PII-CAT constructs, have further confirmed the activation of promoter II by Sp1. In addition, we have identified Sp3, another member of the Sp1 family of transcription factors, as a second factor that can bind to the glucose response elements of PII.
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PMID:Sp1 mediates glucose activation of the acetyl-CoA carboxylase promoter. 857 28

Transcription from the housekeeping promoter for the acetyl coenzyme A carboxylase (ACC) gene, which encodes the rate-controlling enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels through novel binding sites for the sterol-sensitive sterol regulatory element binding protein (SREBP)-1 transcription factor. The position of the SREBP sites relative to those for the ubiquitous auxiliary transcription factor Sp1 is reminiscent of that previously described for the sterol-regulated low density lipoprotein receptor promoter. The experiments provide molecular evidence that the metabolism of fatty acids and cholesterol, two different classes of essential cellular lipids, are coordinately regulated by cellular lipid levels.
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PMID:Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid. 857 12

Cellular cholesterol and fatty acid levels are coordinately regulated by a family of transcriptional regulatory proteins designated sterol regulatory element binding proteins (SREBPs). SREBP-dependent transcriptional activation from all promoters examined thus far is dependent on the presence of an additional binding site for a ubiquitous coactivator. In the low-density lipoprotein (LDL) receptor, acetyl coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) promoters, which are all regulated by SREBP, the coactivator is the transcription factor Sp1. In this report, we demonstrate that Sp3, another member of the Sp1 family, is capable of substituting for Sp1 in coactivating transcription from all three of these promoters. Results of an earlier study showed that efficient activation of transcription from the LDL receptor promoter required domain C of Sp1; however, this domain is not crucial for activation of the simian virus 40 promoter, where synergistic activation occurs through multiple Sp1 binding sites and does not require SREBP. Also in the present report, we further localize the critical determinant of the C domain required for activation of the LDL receptor to a small region that is highly conserved between Sp1 and Sp3. This crucial domain encompasses the buttonhead box, which is a 10-amino-acid stretch that is present in several Sp1 family members, including the Drosophila buttonhead gene product. Interestingly, neither the buttonhead box nor the entire C domain is required for the activation of the FAS and ACC promoters even though both SREBP and Sp1 are critical players. ACC and FAS each contain two critical SREBP sites, whereas there is only one in the LDL receptor promoter. This finding suggested that buttonhead-dependent activation by SREBP and Sp1 may be limited to promoters that naturally contain a single SREBP recognition site. Consistent with this model, a synthetic construct containing three tandem copies of the native LDL receptor SREBP site linked to a single Sp1 site was also significantly activated in a buttonhead-independent fashion. Taken together, these studies indicate that transcriptional activation through the concerted action of SREBP and Sp1 can occur by at least two different mechanisms, and promoters that are activated by each one can potentially be identified by the number of critical SREBP binding sites that they contain.
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PMID:Promoter selective transcriptional synergy mediated by sterol regulatory element binding protein and Sp1: a critical role for the Btd domain of Sp1. 927 97