title: Modelling proteasome and proteasome regulator activities.
abstract: Proteasomes are key proteases involved in a variety of processes ranging from the clearance of damaged proteins to the presentation of antigens to CD8+ T-lymphocytes. Which cleavage sites are used within the target proteins and how fast these proteins are degraded have a profound impact on immune system function and many cellular metabolic processes. The regulation of proteasome activity involves different mechanisms, such as the substitution of the catalytic subunits, the binding of regulatory complexes to proteasome gates and the proteasome conformational modifications triggered by the target protein itself. Mathematical models are invaluable in the analysis; and potentially allow us to predict the complex interactions of proteasome regulatory mechanisms and the final outcomes of the protein degradation rate and MHC class I epitope generation. The pioneering attempts that have been made to mathematically model proteasome activity, cleavage preference variation and their modification by one of the regulatory mechanisms are reviewed here.
authors: Theoretical Systems Biology, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK. juliane.liepe08@imperial.ac.uk.
authors: Juliane
authors: J
authors: Liepe
authors: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. hergo@charite.de.
authors: Herman-Georg
authors: HG
authors: Holzhütter
authors: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. p-m.kloetzel@charite.de.
authors: Peter M
authors: PM
authors: Kloetzel
authors: Theoretical Systems Biology, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK. m.stumpf@imperial.ac.uk.
authors: Michael P H
authors: MP
authors: Stumpf
authors: Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. michele.mishto@charite.de.
authors: Michele
authors: M
authors: Mishto
mesh_terms: D000818:Animals; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D046988:Proteasome Endopeptidase Complex