Journal article
Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes
Juliane Liepe, Hermann-Georg Holzhuetter, Elena Bellavista, Peter M Kloetzel, Michael PH Stumpf, Michele Mishto
ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2015
DOI: 10.7554/eLife.07545
Abstract
Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predi..
View full abstractGrants
Awarded by Biotechnology and Biological Sciences Research Council (BBSRC)
Awarded by Berlin Institute of Health
Awarded by Einstein Stiftung Berlin
Awarded by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) via a David Sainsbury Fellowship
Awarded by Human Frontier Science Program (HFSP)
Awarded by Leverhulme Trust
Awarded by BBSRC
Funding Acknowledgements
[ "Biotechnology and Biological Sciences Research Council (BBSRC) BB/G007934/1 Michael PH Stumpf", "Berlin Institute of Health CRG1-TP1 Peter M Kloetzel", "Einstein Stiftung Berlin A2013-174 Peter M Kloetzel", "National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) via a David Sainsbury Fellowship NC/K001949/1 Juliane Liepe", "Human Frontier Science Program (HFSP) RGP0061/2011 Michael PH Stumpf", "Leverhulme Trust F/07058/BP Michael PH Stumpf", "The Royal Society Wolfson Research Merit Award Michael PH Stumpf", "AICE FIRE Onlus Emilia Romagna Michele Mishto" ]