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Structure and Function of Notch Pathway Transcription Complexes
Dr. Rhett Kovall Department of Molecular Genetics, Biochemistry, and Microbiology
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The Notch pathway is a cell-to-cell signaling mechanism that plays important roles in cell fates decisions throughout the developing and adult organism. Proper pathway regulation is essential, as errant signaling results in congenital defects, cardiovascular disorders, and cancer. Extracellular complexation of Notch receptors with ligands ultimately results in changes in gene expression, which is regulated by the nuclear effector of the pathway, CSL (CBF-1, Su(H), Lag-1). CSL is a DNA binding protein that is involved in both repression and activation of transcription from genes that are responsive to Notch signaling. CSL is converted from a repressor to an activator through the formation of the CSL-NotchIC-Mastermind ternary complex. Here I will describe our structural and functional studies of CSL mediated transcriptions complexes, highlighting our understanding of how an active transcription complex assembles, as well as touch upon our more recent work that characterizes CSL-DNA and CSL-corepressor interactions. |