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Cholesterogenic lanosterol 14alpha-demethylase (CYP51) is an immediate early response geneFink, Martina ...Lanosterol 14alpha-demethylase (CYP51) responds to cholesterol feedback regulation through sterol regulatory element binding proteins (SREBPs). The proximal promoter of CYP51 contains a conserved ... region with clustered regulatory elements: GC box, cAMP-response elements (CRE-like), and sterol regulatory element (SRE). In lipid-rich (SREBP-poor) conditions, the CYP51 mRNA drops gradually, the promoter activity is diminished, and no DNA-protein complex is observed at the CYP51-SRE1 site. The majority of cAMP-dependent transactivation is mediated through a single CRE (CYP51-CRE2). Exposure of JEG-3 cells to forskolin, a mediator of the cAMPdependent signaling pathway, provokes an immediate early response of CYP51, which has not been described before for any cholesterogenic gene. The CYP51 mRNA increases up to 4-fold in 2 h and drops to basal level after 4 h. The inducible cAMP early repressor (ICER) is involved in attenuation of transcription. Overexpressed CRE-binding protein (CREB)/ CRE modulator (CREM) transactivates the mouse/human CYP51 promoters containing CYP51-CRE2 independently of SREBPs, and ICER decreases the CREB-induced transcription. Besides the increased CYP51 mRNA, forskolin affects the de novo sterol biosynthesis in JEG-3 cells. An increased consumption of lanosterol, a substrate of CYP51, is observed together with modulation of the postlanosterol cholesterogenesis, indicating that cAMP-dependent stimuli cross-talk with cholesterol feedback regulation. CRE-2 is essential for cAMPdependent transactivation, whereas SRE seems to be less important. Interestingly, when CREB is not limiting, the increasing amounts ofSREBP-la fail to transactivate the CYP51 promoter above the CREB-only level,suggesting that hormones might have an important role in regulating cholesterogenesis in vivo.Vir: Endocrinology. - ISSN 0013-7227 (Letn. 146, št. 12, 2005, str. 5321-5331)Vrsta gradiva - članek, sestavni delLeto - 2005Jezik - angleškiCOBISS.SI-ID - 20426969
Avtor
Fink, Martina |
Ačimovič, Jure |
Režen, Tadeja |
Tanšek, Nataša |
Rozman, Damjana, 1960-
Teme
Oxidoreductases |
Genetics |
Metabolism |
Genes, Immediate-Early |
Cytochrome P-450 |
Genetics |
Metabolism |
Cholesterol |
Cyclic Amp |
Genetics |
Metabolism |
Trans-Activation (Genetics) |
Time Factors |
Signal Transduction |
Sterols |
Metabolism |
Rna, Messenger |
Metabolism |
Promoter Regions (Genetics) |
Lipids |
Antagonists And Inhibitors |
Tumor Cells, Cultured |
Forskolin |
Pharmacology |
Ciklični AMP |
Citokrom P-450 |
Geni takojšnji-zgodnji |
Holesterol |
Oksidoreduktaze |
Forskolin |
Lipidi |
Promoterska področja (genetika) |
RNA, prenašalna |
Signal, prevajanje |
Steroli |
Trans-aktivacija (genetika) |
Tumorske celične kulture |
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Fink, Martina | 18992 |
Ačimovič, Jure | 28352 |
Režen, Tadeja | 22459 |
Tanšek, Nataša | ![]() |
Rozman, Damjana, 1960- | 06013 |
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