This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The NF-kappaB proteins belong to a family of inducible transcription factors that play a central role in immune and inflammatory responses, apoptosis, cell growth, and cell differentiation. There are five known NFkappaB proteins-p50, p65, p52, RelB, and c-rel which form combinatorial homo- and heterodimers. In response to various stimuli, active NF-kB migrates to the nucleus. Nuclear NF-kappaB then specifically binds a ten base pair DNA motif in the promoters of many response factor genes activating their transcription. The structures of several NF-kappaB dimers bound to DNA have already been solved by our laboratory and others. There is no available structure of a RelB/NF-kappaB heterodimer. Several features of RelB make it a unique NF-kappaB. It does not form homodimers under physiological condition nor can it directly bind to DNA. RelB also contains an amino terminal activating domain, not present in other NF-kappaBs, which is imperative for gene activation. Several in vivo studies have shown that RelB regulation is distinct from other NF-kappaB trans activators. In this proposal, we plan to study the structure of the p50/RelB heterodimer bound to DNA. This study would provide useful insights on the conformational features of this dimer which make it functionally unique.
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