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Biomolecules 2014, 4(2), 585-599; doi:10.3390/biom4020585

Modelling Proteasome and Proteasome Regulator Activities

Theoretical Systems Biology, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK
Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London SW7 2AZ, UK
Interdepartmental Center for Cancer Research "Giorgio Prodi", University of Bologna, 40126 Bologna, Italy
Authors to whom correspondence should be addressed.
Received: 25 March 2014 / Revised: 28 May 2014 / Accepted: 30 May 2014 / Published: 20 June 2014
(This article belongs to the Special Issue Proteasomes and Its Regulators)
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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.
Keywords: proteasome; mathematical model; 11S; 19S; non-catalytic modifier sites proteasome; mathematical model; 11S; 19S; non-catalytic modifier sites
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Liepe, J.; Holzhütter, H.-G.; Kloetzel, P.M.; Stumpf, M.P.H.; Mishto, M. Modelling Proteasome and Proteasome Regulator Activities. Biomolecules 2014, 4, 585-599.

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