Characterization of a neuronal κB-binding factor distinct from NF-κB

Transcription factors that bind κB enhancer elements have begun to garner wide attention in neurobiology. Data suggest that activation of κB- binding factors in neurons can be protective against various neurotoxins, but other data have connected NF-κB to cell death. In electrophoretic mobility shift assays of κB-binding activity, we have found that the predominant activity in rat brain tissue, in primary neurons, and in neuronal cell lines has a mobility inconsistent with that of bona fide NF-κB (RelA-p50 heterodimer). We have tentatively termed this activity neuronal κB-binding factor (NKBF). Competition assays with various DNA probes distinguished NKBF from NF-κB. Probes that efficiently bind the p50 homodimer were able to compete with a conventional NF-κB probe for NKBF binding, but NKBF did not react with antibodies to p50 (or any other known Rel family members). Furthermore, UV-crosslinking indicated that NKBF is composed of two polypeptides of 82 kDa and 27 kDa. Although NKBF activity can be elevated in a manner independent of new macromolecular synthesis, it does not appear to be modulated by IκB. Finally, no NF-κB was induced by glutamate in highly enriched neuronal cultures, although it was induced in neuron-glia cocultures. These data suggest that the primary κB-binding transcription factor in neurons is a novel protein complex distinct from NF-κB.