NRF, a nuclear inhibitor of NF-kappaB proteins silencing interferon-beta promoter.
The family of NF-kappaB/rel transcription factors regulates a variety of promoters through specific DNA-binding sites. Consistent with the role of NF-kappaB activation as a response to pathogens, it regulates the expression of immune modulating cytokines like interferon-beta3 (IFN-3). Transcriptional regulation of IFN-beta is characterized by strict constitutive repression and virus-mediated activation. A nuclear protein, called NRF (NF-kappaB repressing factor) silences constitutively the IFN-beta3 promoter by binding to the negative regulatory element (NRE). This control is achieved by a direct protein-protein interaction between NRF and proximal bound NF-kappaB factors preventing the transcriptional activation. After viral induction NRF still binds but does not any more exert its specific inhibition. NRE-related sequences found in a number of promoters like those of HIV-1, HTLV-1 and the genes of the IL-2Ralpha and IL-8 constitute functionally related silencer elements which repress the constitutive enhancing activity of NF-kappaB/rel-binding sites from these promoters.
Nourbakhsh
M
M
Department of Gene Regulation and Differentiation, GBF, German Research Institute for Biotechnology, Braunschweig, Germany.
Oumard
A
A
Schwarzer
M
M
Hauser
H
H
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; C111027:NKRF protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D016899:Interferon-beta