| Author/Editor | Fink, Martina | |
| Title | Od holesterola neodvisno uravnavanje izražanja človeškega gena za lanosterolno 14alfa-demetilazo (CYP51) | |
| Translated title | Cholesterol-independent regulation of expression of the human lanosterol 14alpha-demethylase gene (CYP51) | |
| Type | monografija | |
| Place | Ljubljana | |
| Publisher | Medicinska fakulteta | |
| Publication year | 2002 | |
| Volume | str. 158 | |
| Language | slo | |
| Abstract | Lanosterol 14alpha-demethylase (CYP51) is involved in the housekeeping process of cholesterol biosynthesis in animals. The promoter/regulatory regions of mammalian CYPSI genes are highly evolutionary conserved and contain several regulatory DNA sequences: cAMP responsive elements (CRE), sterol regulatory element (SRE) and GC-box. The goal of our study was to evaluate interactions between the cAMP-dependent and sterol-dependent signalling pathways in regulation of lanosterol 14alpha-demethylase (CYPSIJ and to study the cholesterol-independent regulation of expression of the human CYPSI gene expression. We established that CRE2 and SRE1 regulatory elements are active in in vitro and ex vivo conditions. SREBP, GC-box binding proteins and CREB like proteins bind to the human CYPSI promoter simultaneously in in vitro conditions. Overexpression of PKA activated SREBP- dependent transcription, while CREB dependent transcription was unaffected. Protein-protein interactions between the cAMP-dependent and sterol-dependent transcription factors are essential for CYPSJ expression. Experiments with deletion CATconstructs indicated that region -334/-121 is necessary for basal, cAMP-dependent and also for sterol-dependent CYPSI gene expression. Transient transfections with the human CYPSJ promoter with mutated CRE2 or SRE1 elements indicated that both elements are important for basal expression and also for SREBP-dependent expression of CYPSI, while SRE1 is not essential for cAMP-dependent transcription. Presence of functional CRE2 is essential for sterol-dependent transcription of human CYPSJ. (Abstract truncated at 2000 characters). | |
| Descriptors | CYCLIC AMP-DEPENDENT PROTEIN KINASES CYTOCHROME P-450 PROMOTER REGIONS (GENETICS) LANOSTEROL CYCLIC AMP RECOMBINANT PROTEINS PLASMIDS DNA, BACTERIAL SEQUENCE ANALYSIS, DNA SEQUENCE ANALYSIS, RNA DNA-BINDING PROTEIN, CYCLIC AMP-RESPONSIVE TRANSFECTION BLOTTING, NORTHERN BLOTTING, WESTERN ELECTROPHORESIS, POLYACRYLAMIDE GEL |