Title: Ubiquitin-dependent Proteolysis: Specificity and Mechanism.
Post-translational ubiquitination of proteins generates a signal that targets the modified protein to multiple cellular fates. Polyubiquitin binding proteins are necessary to couple the polyubiquitin signal to downstream cellular events such as endocytosis, degradation of cell cycle proteins, receptor signaling, and DNA repair. Each of those processes uses a different form of polyubiquitin and presumably employs different specific binding receptors.. We will synthesize a panel of differently linked non-hydrolyzable polyubiquitin analogs to use as affinity supports to identify specific polyubiquitin receptors. This work will identify specific polyubiquitin binding proteins and enhance our understanding of the numbers and specificity of these receptors.