Neuronal kappa B-binding factors consist of Sp1-related proteins. Functional implications for autoregulation of N-methyl-D-aspartate receptor-1 expression.
Neurons contain a protein factor capable of binding DNA elements normally bound by the transcription factor NF-kappaB. However, several lines of evidence suggest that this neuronal kappaB-binding factor (NKBF) is not bona fide NF-kappaB. We have identified NKBF from cultures of neocortical neurons as a complex containing proteins related to Sp1. This complex was bound by antibodies to Sp1, Sp3, and Sp4 and was competed from binding to an NF-kappaB element by an oligonucleotide containing an Sp1-binding site. This Sp1 oligonucleotide detected an abundant factor in neuronal nuclei that migrated in electrophoretic mobility shift assays at a position consistent with NKBF. Expression of transfected Sp1 stimulated transcription in a manner dependent upon a kappaB cis-element. Similar to our previous reports for NKBF (Mao, X., Moerman, A. M., Lucas, M. M., and Barger, S. W. (1999) J. Neurochem. 73, 1851-1858 and Moerman, A. M., Mao, X., Lucas, M. M., and Barger, S. W. (1999) Mol. Brain Res. 67, 303-315), the activity of the Sp1-related factor was reduced by activation of ionotropic glutamate receptors, consistent with proteolytic degradation of all three Sp1-related factors. Expression of the N-methyl-d-aspartate receptor-1 (NR1) subunit of glutamate receptors correlated with the activity of the Sp1-related factor, specifically through an Sp1 element in the NR1 promoter. These data provide the first evidence that Sp1 or related family members are responsible for kappaB-binding activity and are involved in a negative feedback for NR1 in central nervous system neurons.
Mao
Xianrong
X
Department of Anatomy and Neurobiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Moerman
Andrea M
AM
Barger
Steven W
SW
D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D017930:Genes, Reporter; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004247:DNA; D004268:DNA-Binding Proteins; D018698:Glutamic Acid; D016328:NF-kappa B; D009841:Oligonucleotides; D016194:Receptors, N-Methyl-D-Aspartate; D016329:Sp1 Transcription Factor