RRC ID |
38715
|
著者 |
Umayahara Y, Kawamori R, Watada H, Imano E, Iwama N, Morishima T, Yamasaki Y, Kajimoto Y, Kamada T.
|
タイトル |
Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer.
|
ジャーナル |
J Biol Chem
|
Abstract |
As a step toward elucidating the physiological role of insulin-like growth factor-I (IGF-I) in mediating estrogen action, we sought to determine the molecular basis of the phenomenon. In HepG2 cells expressing exogenous estrogen receptors (ER), a reporter gene plasmid containing 600 base pairs of the chicken IGF-I promoter enhanced expression of luciferase 8.6-fold in response to 10(-6) M 17 beta-estradiol, indicating that the IGF-I promoter is a target of estrogen regulation. Although no conventional estrogen-responsive element was identified within the promoter fragment, the AP-1 motif located therein was shown to be essential; the estrogen-responsive enhancement of the Fos-Jun binding to the AP-1 motif, which takes place by means of post-translational modification, mediates the estrogen action. A direct or indirect interaction between the estrogen-ER complex and the Fos-Jun complex seems to facilitate the Fos-Jun binding to the target DNA. Although ER binding to the target DNA was not considered to be involved in the signaling pathway, the DNA binding domain-deficient ER did not mediate the phenomenon, providing support for the existence of a unique function of the DNA binding domain of ER in facilitating some protein-protein interaction. In conclusion, our present observations demonstrate that the chicken IGF-I gene promoter is controlled by estrogen through a unique pathway involving Fos, Jun, and the DNA binding domain of ER.
|
巻・号 |
269(23)
|
ページ |
16433-42
|
公開日 |
1994-6-10
|
PII |
S0021-9258(17)34025-5
|
PMID |
8206951
|
MeSH |
Animals
Base Sequence
Cells, Cultured
Chickens
DNA Mutational Analysis
Enhancer Elements, Genetic / genetics*
Estradiol / pharmacology*
Gene Expression Regulation / drug effects*
Gene Transfer Techniques
Genes, Reporter
Humans
Insulin-Like Growth Factor I / biosynthesis*
Insulin-Like Growth Factor I / genetics
Luciferases / biosynthesis
Luciferases / genetics
Molecular Sequence Data
Promoter Regions, Genetic / genetics
Protein Binding
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism*
Receptors, Estrogen / metabolism
Signal Transduction
Transcription, Genetic*
|
IF |
4.238
|
引用数 |
308
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
Hep G2(RCB0459) |