Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 10, Pages 6156-6168Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M807713200
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Funding
- National Institutes of Health [GM60852]
- Oregon State University College of Pharmacy
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The orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) plays key roles in development and homeostasis. A tandem affinity purification procedure revealed that COUP-TFI associated with a number of transcriptional regulatory proteins in HeLa S3 cells, including the nuclear receptor corepressor (NCoR), TIF1 beta/KAP-1, HDAC1, and the SWI/SNF family member Brahma. The proapoptotic protein DBC1 was also identified in COUP-TFI complexes. In vitro experiments revealed that COUP-TFI interacted directly with NCoR but in a manner different from that of other nuclear receptors. DBC1 stabilized the interaction between COUP-TFI and NCoR by interacting directly with both proteins. The gene encoding the anti-apoptotic protein TNFAIP8 (tumor necrosis factor alpha(TNF alpha)-induced protein 8) was identified as being repressed by COUP-TFI in a manner that required several of the component proteins of the COUP-TFI complex. Finally, our studies highlight a central role for COUP-TFI in the induction of the TNFAIP8 promoter by TNF alpha. Together, these studies identify a novel COUP-TFI complex that functions as a repressor of transcription and may play a role in the TNF alpha signaling pathways.
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