NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the α-helical region of the STAT5 transactivation domain
- Signal transducer and activator of transcription 5 (STAT5) is a transcription factor that activates prolactin (PRL)-dependent gene expression in the mammary gland. For the activation of its target genes, STAT5 recruits coactivators like p300 and the CREB-binding protein (CBP). In this study we analyzed the function of p300/CBP-associated members of the p160/SRC/NCoA-family in STAT5-mediated transactivation of β-casein expression. We found that only one of them, NCoA-1, acts as a coactivator for both STAT5a and STAT5b. The two coactivators p300/CBP and NCoA-1 cooperatively enhance STAT5a-mediated transactivation. For NCoA-1-dependent coactivation of STAT5, both the activation domain 1 and the amino-terminal bHLH/PAS domain are required. The amino-terminal region mediates the interaction with STAT5a in cells. A motif of three amino acids in an α-helical region of the STAT5a-transactivation domain is essential for the binding of NCoA-1 and for the transcriptional activity of STAT5a. Moreover we observed that NCoA-1 is involved in the synergistic action of the glucocorticoid receptor and STAT5a on the β-casein promoter. These findings support a model in which STAT5, in concert with the glucocorticoid receptor, recruits a multifunctional coactivator complex to initiate the PRL-dependent transcription.
Verfasserangaben: | Claudia M. LitterstGND, Stefanie KliemGND, Dominique Marilley, Edith PfitznerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-761073 |
DOI: | https://doi.org/10.1074/jbc.M303644200 |
ISSN: | 0021-9258 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/12954634 |
Titel des übergeordneten Werkes (Englisch): | Journal of biological chemistry |
Verlag: | American Society for Biochemistry and Molecular Biology Publications |
Verlagsort: | Bethesda, Md |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 04.01.2021 |
Jahr der Erstveröffentlichung: | 2003 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 21.09.2023 |
Jahrgang: | 278 |
Ausgabe / Heft: | 46 |
Seitenzahl: | 12 |
Erste Seite: | 45340 |
Letzte Seite: | 45351 |
HeBIS-PPN: | 513165983 |
Institute: | Medizin |
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus | |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |