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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


  • Litterst CM
  • Kliem S
  • Marilley D
  • Pfitzner E


The Journal of biological chemistry

Publication Data

November 14, 2003

Associated Grants


Mesh Terms

  • 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