STRUCTURE/FUNCTION STUDIES OF NUCLEAR FACTOR KAPPA B

University Of California San Diego, La Jolla CA

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Abstract

DESCRIPTION: The Rel homology proteins are a class of transcription factors involved in the rapid response of the cell to external stress, of which the prototypical member is the nuclear factor Kappa B (NFkB). A number of different Rel family proteins have been identified, and they share a region of sequence similarity that spans approximately 300 amino acids that is known as the Rel Homology Region (RHR). A key feature of the regulation of transcription by Rel family proteins is the formation of different homo- and hetero-dimers that differ in their intrinsic stabilities and in their ability to promote transcription from different target sites. This proposal is aimed at further understanding the molecular basis for dimerization and DNA recognition, and builds on the previous crystal structure analysis of p50 RHR homodimersin complex with DNA, determined in the laboratories of Paul Sigler and Steve Harrison. Dr. Ghosh carried out the structure determination of the p50 homodimer on DNA while a post-doc in Paul Sigler's laboratory. He states that Dr. Sigler will not be carrying on work on this project, and Dr. Ghosh is continuing the analysis of the Rel family after having taken on a faculty position at UCSD.