The majority of targeted protein degradation in the cell is performed by the ubiquitin (Ub)/26S proteasome pathway, which is highly conserved in all eukaryotic species. In this pathway, proteins to be degraded are covalently tagged with multiple ubiquitins, which serves as the degradation signal, by the sequential action of three enzymes. The final enzyme in this process, the E3 Ub-ligase, binds the target and catalyzes attachment of the Ub moiety to the protein. This proteolytic pathway has been shown to be important for a wide range of cellular processes, including cell cycle progression, DNA repair, hormone signal transduction and receptor regulation, and degradation of abnormal proteins. It also has been implicated genetically in a number of diseases, including cancer, Parkinson's disease, and muscular dystrophy, arguing for the need to study this pathway in more detail. One subfamily of E3 Ub-ligases is the SCF (Skpl, Cullin/Cdc53, F-box protein) complex. In Arabidopsis thaliana 19 genes encode Skpl homologues and 694 genes encode F-box proteins. Presumable the 19 ASKs combine with the 694 F-box proteins to generate a hierarchy of SCF complexes capable of labeling a wide range of targets. I propose a line of research that studies the functions of the ASK genes in Arabidopsis. By using genetic, biochemical, and cytological approaches to characterize the function of ASKs, I hope to better understand the roles that SCF complexes play in various cellular processes in Arabidopsis. The remarkable conservation of the Ub/26S proteasome pathway means these studies should contribute to our understanding of its function in all eukaryotes, which could lead to new strategies to affect the pathway for medicinal or agricultural benefit.
| Christians, Matthew J; Gingerich, Derek J; Hua, Zhihua et al. (2012) The light-response BTB1 and BTB2 proteins assemble nuclear ubiquitin ligases that modify phytochrome B and D signaling in Arabidopsis. Plant Physiol 160:118-34 |
| Christians, Matthew J; Gingerich, Derek J; Hansen, Maureen et al. (2009) The BTB ubiquitin ligases ETO1, EOL1 and EOL2 act collectively to regulate ethylene biosynthesis in Arabidopsis by controlling type-2 ACC synthase levels. Plant J 57:332-45 |
| Gingerich, Derek J; Hanada, Kousuke; Shiu, Shin-Han et al. (2007) Large-scale, lineage-specific expansion of a bric-a-brac/tramtrack/broad complex ubiquitin-ligase gene family in rice. Plant Cell 19:2329-48 |
| Gingerich, Derek J; Gagne, Jennifer M; Salter, Donald W et al. (2005) Cullins 3a and 3b assemble with members of the broad complex/tramtrack/bric-a-brac (BTB) protein family to form essential ubiquitin-protein ligases (E3s) in Arabidopsis. J Biol Chem 280:18810-21 |
