Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated positive and negative autoregulation.
NF-kappa B is an inducible transcription factor complex which regulates the expression of a variety of genes which are involved in the immune, inflammatory, and acute-phase responses. The maintenance of NF-kappa B activity in stimulated cells requires ongoing protein synthesis, suggesting several modes of regulation. In this report, we have characterized the transcriptional regulation of one family member, NF-kappa B2. The genomic structure and sequence of NF-kappa B2 revealed the presence of two promoters and at least four kappa B regulatory elements, which mediate responsiveness to phorbol myristate acetate and tumor necrosis factor alpha. Similar to other NF-kappa B family members, NF-kappa B2 is positively autoregulated. In contrast to other family members, we find that kappa B elements in the NFKB2 promoter can also mediate transcriptional repression in the absence of NF-kappa B. We identified a nuclear complex which binds specifically to a subset of kappa B-related sites but not to the canonical kappa B element. Because of its putative inhibitory or repressive effect, this binding activity has been termed Rep-kappa B. This mechanism of repressing basal NF-kappa B2 transcription in an inactivated state enables the cell to tightly control NF-kappa B2 activity. These data demonstrate that a novel mode of kappa B-dependent regulation is mediated by specific kappa B sites in the NFKB2 promoter.
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650.
S
S
Liptay
R M
RM
Schmid
E G
EG
Nabel
G J
GJ
Nabel
D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics*; D052003:NF-kappa B p52 Subunit; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014158:Transcription, Genetic
D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008934:Mitogens; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D009687:Nuclear Proteins