Heat Shock Factor 1 Represses Transcription of the IL-1β Gene through Physical Interaction with the Nuclear Factor of Interleukin 6

Heat shock factor (HSF) 1 is the major heat shock transcription factor that regulates stress-inducible synthesis of heat shock proteins and is also essential in protection against endotoxic shock. Following our previous study, which demonstrated the transcriptional repression of the IL-1β gene by HS...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-04, Vol.277 (14), p.11802-11810
Main Authors: Xie, Yue, Chen, Changmin, Stevenson, Mary Ann, Auron, Philip E., Calderwood, Stuart K.
Format: Article
Language:English
Subjects:
HSF1 protein
IL-1^b gene
NF-IL6 protein
Spi.1 protein
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Summary:Heat shock factor (HSF) 1 is the major heat shock transcription factor that regulates stress-inducible synthesis of heat shock proteins and is also essential in protection against endotoxic shock. Following our previous study, which demonstrated the transcriptional repression of the IL-1β gene by HSF1 (Cahill, C. M., Waterman, W. R., Xie, Y., Auron, P. E., and Calderwood, S. K. (1996) J. Biol. Chem. 271, 24874–24879), we have examined the mechanisms of transcriptional repression. Our studies show that HSF1 represses the lipopolyliposaccharide-induced transcription of the IL-1β promoter through direct interaction with the nuclear factor of interleukin 6 (NF-IL6, also known asCCAAT enhancer bindingprotein (C/EBPβ), an essential regulator in IL-1β transcription. We show for the first time that HSF1 binds directly to NF-IL6 in vivo and antagonizes its activity. The HSF1/NF-IL6 interaction involves a sequence of HSF1 containing the trimerization and regulatory domains and the bZip region of NF-IL6. HSF1 has little effect on IL-1β promoter activity stimulated by the essential monocytic transcription factor Spi.1 but is strongly inhibitory to transcriptional activation by NF-IL6 and to the synergistic activation by NF-IL6 and Spi.1. Because of its ability to bind to specific C/EBP elements in the promoters of multiple genes and its ability to interact with other transcription factors, NF-IL6 is involved in transcriptional regulation of a wide range of genes. Interaction between HSF1 and NF-IL6 could thus be an important mechanism in HSF1 regulation of general gene transcription during endotoxin stress.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109296200