RRC ID 38715
Author Umayahara Y, Kawamori R, Watada H, Imano E, Iwama N, Morishima T, Yamasaki Y, Kajimoto Y, Kamada T.
Title Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer.
Journal 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.
Volume 269(23)
Pages 16433-42
Published 1994-6-10
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 4.106
Times Cited 308
Human and Animal Cells