Coactivators in gene regulation by STAT5.
Signal transducer and activator of transcription 5 (STAT5) is a member of the STAT family of transcription factors that relay the effect of diverse cytokines, hormones, and growth factors by regulating the transcription of distinct target genes. This function is emphasized by its crucial role in the development of the mammary gland and the hematopoietic system. Cytokine receptor-associated Janus kinases (JAKs) induce dimerization, nuclear translocation, and DNA binding through tyrosine phosphorylation of STAT5. STAT5 regulates the expression of cytokine target genes by binding to gamma interferon-activated sequence (GAS) motifs. Transcriptional activation requires the contact of STAT5 to coactivators and components of the transcription machinery. Another important point in transcriptional activation is the cooperation with other transcription factors that bind in close vicinity to the target gene promoters and enhancers. Their concerted action can result in an enhanced binding to the promoters or in cooperative recruitment of coactivators. In addition, cross-talk with other signaling pathways as well as secondary modifications of STAT5 have been described to affect transactivation function.
Litterst
Claudia M
CM
Georg-Speyer-Haus, Institute for Biomedical Research, D-60596 Frankfurt, Germany.
Kliem
Stefanie
S
Lodrini
Marco
M
Pfitzner
Edith
E
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008894:Milk Proteins / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004247:DNA