STUDY OF INTERACTION BETWEEN NF-κB DIMERS

Abstract

NF-κB, or Nuclear factor kappa-light-chain-enhancer of activated B cells, are a family of transcription factors that regulates the expression of κB light chains in mature B cells and plasma cells. These proteins have roles in immune and stress response, apoptosis, development, etc. In mammals, they include five proteins, namely RelA, RelB, c-Rel, p50 and p52, that share a well conserved ~300 amino acid residue long Rel homology domain. These proteins are regulated by inhibitory proteins known as inhibitor of κB (IκB proteins). They can generate more than 12 dimers recognizing 9-11 nucleotide long κB sites. Each dimer selectively regulates a few target promoters. Some genes are redundantly induced by more than one dimer but the transformation efficiency varies. Homodimers of p50 and p52 lack Trans activation domain and for that they act as repressors. Those repressed genes can be activated in two possible ways, one is by exchanging the monomers and another is by recruiting co-activator proteins. We aim to study the dynamics of exchange of monomers on DNA and the role of H-bonds in formation of rare dimers using Nuclear Magnetic Resonance spectroscopy.