Estrogen Receptor α and the Activating Protein-1 Complex Cooperate during Insulin-like Growth Factor-I-induced Transcriptional Activation of the pS2/TFF1 Gene
Autor: | Patrick Balaguer, Aurélie Escande, Sylvain Baron, Kerstin Bystricky, Géraldine Albérola, Hélène Richard-Foy |
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Přispěvatelé: | Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2007 |
Předmět: |
Transcriptional Activation
Proto-Oncogene Proteins c-jun Response element Chromatin Remodeling Factor Biology Transfection Models Biological Biochemistry Cell Line Tumor Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Insulin-Like Growth Factor I Phosphorylation Binding site Molecular Biology Transcription factor Estrogen receptor beta Regulation of gene expression Tumor Suppressor Proteins DNA Helicases Estrogen Receptor alpha Nuclear Proteins Cell Biology Molecular biology Gene Expression Regulation Neoplastic Transcription Factor AP-1 AP-1 transcription factor Trefoil Factor-1 Proto-Oncogene Proteins c-fos Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Protein Binding Transcription Factors |
Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2007, 282 (16), pp.11732-41 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.m610079200 |
Popis: | Insulin like growth factor I (IGF-I) displays estrogenic activity in breast cancer cells. This activity is strictly dependent on the presence of estrogen receptor alpha (ERalpha). However the precise molecular mechanisms involved in this process are still unclear. IGF-I treatment induces phosphorylation of the AF1 domain of ERalpha and activation of estrogen regulated genes. These genes are characterized by important differences in promoter architecture and response element composition. We show that promoter structure is crucial for IGF-I-induced transcription activation. We demonstrate that on a complex promoter such as the pS2/TFF1 promoter, which contains binding sites for ERalpha and for the activating protein-1 (AP1) complex, transcriptional activation by IGF-I requires both ERalpha and the AP1 complex. IGF-I is unable to stimulate transcription of an estrogen-regulated gene under the control of a minimal promoter containing only a binding site for ERalpha. We propose a molecular mechanism with stepwise assembly of the AP1 complex and ERalpha during transcription activation of pS2/TFF1 by IGF-I. IGF-I stimulation induces rapid phosphorylation and an increase in protein levels of the AP1 complex. Binding of the phosphorylated AP1 complex to the pS2/TFF1 promoter allows recruitment of the chromatin remodeling factor Brg1 followed by binding of ERalpha via its interaction with c-Jun. |
Databáze: | OpenAIRE |
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