轉錄因子SF1、AP1及CREB調控CYP11A1基因啟動子活性之作用機轉
Date Issued
2002
Date
2002
Author(s)
郭應誠
DOI
902320B002158
Abstract
Expression of the human CYP11A1 gene, encoding cytochrome P450scc that
catalyzes the first and rate-limiting step of steroid biosynthesis, is controlled by cAMP
signaling in a tissue-specific manner. To investigate the tissue-selective cAMP
responsiveness of the human CYP11A1 gene, we characterized the functions of elements
in the upstream cAMP-responsive sequences. The electrophoretic mobility shift assay
demonstrated that two CRE/TRE-like elements formed stable complexes with Y1 and
JEG-3 nuclear proteins of the Jun family in cAMP-dependent manner. One additional
element was recognized by SF-1 present in Y1 but absent in JEG-3 cells. Although none
of the binding elements alone was sufficient to mediate cAMP stimulation on the
heterologous tk promoter, site-directed mutagenesis of these elements in the 2.3-kb
CYP11A1 promoter led to reduced response to cAMP stimulation in transient transfections.
Impairment of CYP11A1 promoter activity was also observed in transgenic mutant mice.
Combined mutation of both CRE/TRE-like elements caused complete loss of hormonal
responses in transgenic adrenal glands and testes. In conclusion, the cooperation of two
CRE/TRE-like and SF-1-binding elements defined the cAMP-stimulated, tissue-specific
CYP11A1 promoter activity both in vitro and in vivo.
Subjects
CYP11A1
P450scc
cholesterol side-chain cleavage
steroidogenesis
SF-1
adrenal
NR5A1
cAMP
AP-1
Publisher
臺北市：國立臺灣大學獸醫學系暨研究所
Type
report
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