Regulation of 26S proteasome compartmentalization in yeast

• Applicant: Professorin Dr. Cordula Enenkel
• Subject Area: Cell Biology
• Term: from 2004 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5444399

26S proteasomes are multisubunit key proteases which occur in the cytoplasm and nucleoplasm of eukaryotic cells. Temporally and spatially regulated protein turnover by proteasomes is crucial for cell life and failure in protein degradation leads to disease and cancer. 26S proteasomes consist of proteolytically active core and regulatory particles. The key question is how proteasomal proteolysis is regulated starting with the biogenesis of the holoenzyme in different subcellular compartments. To address this question we chose yeast as model organism, in which a predominant fraction of 26S proteasomes is nuclear. We found that 26S proteasomes are imported into the nucleus as subcomplexes and are finally assembled into the holocomplex. We now want to investigate how the balance of nuclear and cytoplasmic proteasome assembly and distribution is regulated. Therefore, proteasomal subcomplexes of both compartments will be analyzed with regard to different posttranslational modifications such as phosphorylation, which may determine their subcellular localization. Furthermore, our preliminary data turned our attention to Blm3 and Ecm29, two high molecular mass proteins with structural homologs in mammals, which seem to be involved in nuclear 26S proteasome assembly.

• DFG Programme: Research Grants