Reagents for antagonizing the protein-protein interaction between Raf-1 and apoptosis signal-regulating kinase and uses therefor

摘要

The present invention identifies a novel protein-protein interaction between Raf-1 and apoptosis signal-regulating kinase 1, thereby identifying a molecular basis for cross-talk between the Raf-1-mediated signaling and ASK-1-meditated apoptotic signaling. The invention provides methods for screening for agents that are capable of disrupting the disclosed protein-protein interaction or which are capable of modulating ASK1-mediated apoptosis. The invention further provides Raf-1 binding polypeptides, derived from the N-terminal regulatory domain of ASK1, that find utility as therapeutic agents, as reagents for establishing screening assays, as an immunogens to elicit peptide specific antibodies and as paradigmatic agents for the design or identification of small molecules that share a sufficiently similar structure so as to inhibit or promote the disclosed ASK1/Raf-1 interaction.