The selective degradation of cellular proteins is essential for the growth development, and well being of all living organisms. The protein ubiquitin is an integral part of one major proteolytic pathway which is highly conserved in all eukaryotic species. The specific degradation of proteins by the ubiquitin-dependant proteolytic pathway involves two major recognition steps. In the first step, the protein to be degraded is recognized by a key enzyme in the pathway, the ubiquitin ligase, whereupon the targeted protein is covalently modified with multiple ubiquitins. In the second step, the ubiquitinated protein is recognized by the 26S proteasome and degraded. The importance of this proteolytic pathway is underscored by its function in such diverse processes as cell cycle progression, DNA repair, peroxisome biogenesis, antigen presentation, protein trafficking and the degradation of abnormal proteins. The fact that various diseases appear to block normal ubiquitin pathway function argues the need to study the pathway in order to discover new methods of treatments when the pathway fails. The study proposed here is to isolate and characterize mutants in one subfamily of ubiquitin ligases, the large monomeric HECTs, from the model genetic plant Arabidopsis thaliana. Given the remarkable conservation of the Ub/26S proteasome pathway in all eukaryotes, this will not only define the functions of HECT-E3s in plants but also help us understand their basic roles in the eukaryotic cell and in human health. Ultimately, the study will contribute new strategies to affect the pathway for medicinal benefit.
| Downes, Brian P; Saracco, Scott A; Lee, Sang Sook et al. (2006) MUBs, a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation. J Biol Chem 281:27145-57 |
