NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-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 beta-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 alpha-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 beta-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.
Pubmed ID: 12954634 RIS Download
Amino Acid Motifs | Animals | CREB-Binding Protein | Caseins | Cell Line | Cells, Cultured | Chromatin | DNA-Binding Proteins | Dose-Response Relationship, Drug | HeLa Cells | Histone Acetyltransferases | Humans | Luciferases | Mice | Milk Proteins | Models, Genetic | Nuclear Proteins | Nuclear Receptor Coactivator 1 | Plasmids | Precipitin Tests | Prolactin | Promoter Regions, Genetic | Protein Binding | Protein Structure, Tertiary | Receptors, Glucocorticoid | STAT5 Transcription Factor | Trans-Activators | Transcription Factors | Transcription, Genetic | Transcriptional Activation | Transfection | Tumor Suppressor Proteins