| Abstract: | ["The biogenesis of membrane proteins involves a complex series of steps that range from synthesis, targeting, insertion, folding, and assembly. Failure at any of these steps results in the production of an aberrant product that must be degraded by the cell. Failure to recognize or degrade aberrant membrane proteins can lead to their accumulation, cell dysfunction, and in some cases, disease. We therefore have been focused on determining how at each step in biosynthesis, failed products are discriminated from correct products to selectively target the former for degradation by the ubiquitin proteasome system. Using a biochemical approach, we have been able to reconstitute several of these ubiquitination pathways including stalled translation products on the ribosome, mis-targeted membrane proteins, and aberrant membrane inserted products. These studies are beginning to provide insights into the mechanistic basis of client discrimination and quality control of membrane proteins."] |
