Project Details
Projekt
Biochemical and functional analysis of multicatalytic proteinase subtypes in 20S and 26S proteasoms
Applicant
Professor Dr. Burkhardt Dahlmann
Subject Area
Biochemistry
Term
from 2000 to 2006
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5249988
The proteasome system is involved in very different cellular pathways like removal of misfolded proteins, antigen processing, regulation of cell cycling, and signal transduction. We demonstrate that the core particle of the proteasome system, the 20S proteasome, can be separated in a number of subpopulations. We want to address the question, whether these different subpopulations are specialized subtypes for the various functions of the proteasome system.We will resolve the spectrum of proteasome subpopulations from human erythrocytes and HeLa cells to characterize their subunit composition and posttranslational modifications in correlation with their enzymatic activities. An important point is to find out, whether certain subtypes of proteasomes are located in confined cellular compartments and whether the divers proteasome complexes ( e.g. 26S proteasomes, proteasome-PA28 complexes) contain different proteasome subtypes. Preliminary data suggest that the proteolytic activities of the various proteasome subtypes and their impairement by inhibitors are different. Therefore, we will characterize the subtypes with regard to their cleavage specificity and susceptibility to different proteasomal inhibitors, to find out whether there are selective inhibitors and to get knowledge about their specific functions.Additionally, highly purified subpopulations may facilitate the cristallization of mammalian 20S proteasomes to get further insight into their structure and function.
DFG Programme
Priority Programmes
