Author/Editor     Fink, Martina
Title     Odziv človeškega gena za lanosterolno 14alfa-demetilazo na cAMP odvisno in od sterolov odvisno uravnavanje
Type     monografija
Place     Ljubljana
Publisher     Medicinska fakulteta
Publication year     2000
Volume     str. 79
Language     slo
Abstract     Lanosterol 14alpha-demethylase (CYP51) is the most conserved member of the cytochrome P450 gene superfamily. Enzymes with CYP51 activity are found in all eucaryotic phyla and also in one bacteria (Mycobacterium tuberculosis). CYP51 is a part of a housekeeping process of cholesterol biosynthesis in animals. It removes 14alpha-methyl group from lanosterol producing FF-MAS. MAS (meiosis activating sterols) are intermediates in cholesterol biosynthetic pathway in somatic cells while in germ cells (ovary and testis) they accumulate. MAS sterols can in in vitro conditions reinitiate meiosis in mouse oocytes. CYP51 is ubiquitously expressed with the highest level in testis. In the promoter regulatory regions of mammalian (human, rat, mouse) CYP51 genes conserved regulatory DNA sequences - cAMP responsive elements (CRE1, CRE2, CRE3) and sterol regulatory elements (SRE1 and SRE2) were identified suggesting that both cAMPdependent and sterol-dependent types of regulation may control expression of CYP51. In human, rat and mouse different CYP51 transcripts have been identified. The longer are expressed in all tissues, while the shortest are expressed only in testis of sexullaly mature animals. Somatic transcripts and shorter testis specific transcripts have been identified in all studied mammals. Appearance of the shortest transcripts in mouse and human coincides with the appearance of CREMt protein, a well known inducer of numerous germ cell specific genes. Mobility shift experiments have confirmed that all three cAMP reponsive elements (CRE1, CRE2, CRE3) present in human CYP51 promoter bind cAMP responsive transcription factors. Human CYPS1 CRE1 and CRE2 interact with transcription factors present in somatic cell nuclear extracts as well as in male germ cells. Recombinant human sterol regulatory element binding proteins (SREBP) can in in vitro conditions bind to SRE1 element. (Abstract truncated at 2000 characters.)
Descriptors     LANOSTEROL
CYTOCHROME P-450
GENES, REGULATOR
CYCLIC AMP
STEROLS
RATS
TRANSFECTION
GERM CELLS
TESTIS
RECOMBINANT PROTEINS