Probing the transcriptional machinery with short peptide ligands

BIOL 147

Chinmay Y. Majmudar, chinmay@umich.edu1, Jenifer K Lum, lumj@umich.edu2, and Anna K. Mapp, amapp@umich.edu1. (1) Department of Chemistry, University of Michigan, 930 N University, Ann Arbor, MI 48109-1055, (2) Department of Medicinal Chemistry and Department of Chemistry, University of Michigan, 930 N University, Ann Arbor, MI 48109-1055
Protein-protein interactions play a key role in proper cellular function. Gene-specific transcription is one such event that relies on transcriptional activator proteins to recruit an array of proteins constituting the transcriptional machinery to binding sites proximal to a gene in order to initiate gene transcription. The functional relevance of specific activator protein-transcriptional machinery contacts remains largely unknown. To better define these interactions, we screened a synthetic peptide library against the mediator component Med15 and isolated ligands that specifically targeted this protein. In functional assays we found that these ligands moderately activated transcription and their function depended on the presence of Med15. To generate more potent artificial activators, ligands isolated for Tra1, another target of natural activators are being evaluated for their ability to activate transcription in yeast. Further, combinations of these ligands with the Med15 specific ligands will be used to probe if synergistic activation can be achieved by simultaneously targeting these two proteins.

 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006