Different proteasome subtypes in a single tissue exhibit different enzymatic properties 1 1Edited by R. Huber

Dahlmann, Burkhardt; Ruppert, Thomas; Kuehn, Lothar; Merforth, Simone; Kloetzel, Peter‐M.

doi:10.1006/jmbi.2000.4185

Cited by 186 publications

(207 citation statements)

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“…Since this is a very quick process, many intermediate forms can be observed (71), showing large variation in fragment length produced by the cell during protein degradation. The average length of fragments produced by a proteasome containing all three bi-subunits, the immunoproteasome, is about 8-10 amino acids, and thus ideal for being presented as antigen by the MHC I molecules on the surface of infected cells (72,73).…”

Section: The Proteasomementioning

confidence: 99%

The proteasome and its role in the degradation of oxidized proteins

2008

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SummaryThe generation of free radicals and the resulting oxidative modification of cell structures are omnipresent in mammalian cells. This includes the permanent oxidation of proteins leading to the disruption of the protein structure and an impaired functionality. In consequence, these oxidized proteins have to be removed in order to prevent serious metabolic disturbances. The most important cellular proteolytic system responsible for the removal of oxidized proteins is the proteasomal system. For normal functioning, the proteasomal system needs the coordinated interaction of numerous components. This review describes the fundamental functions of the 20S ''core'' proteasome, its regulators, and the roles of the proteasomal system beyond the removal of oxidized proteins in mammalian cells. IUBMBIUBMB Life, 60(11): 743-752, 2008

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Section: The Proteasomementioning

confidence: 99%

The proteasome and its role in the degradation of oxidized proteins

2008

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“…The 20S proteasome consists of 14 different protein subunits (Groll et al1997), of which only three have an active site (Groll et al 1997(Groll et al , 1999Heinemeyer et al 1997;Tanaka and Kasahara 1998) Tanaka and Kasahara 1998). Thus two forms of proteasome exist: the "immunoproteasome", which is expressed in cells stimulated by gamma interferon (IFN-g) or tumor necrosis factor alpha (TNF-a), and in primary and secondary lymphoid organs, and the "constitutive proteasome", which is expressed in healthy, normal tissues and in immune-privileged organs such as the brain (Dahlmann et al 2000;Noda et al 2000;Kuckelkorn et al 2002). During an antiviral or antibacterial immune response, immunoproteasomes largely replace constitutive proteasomes (Khan et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis of functional differences between the immunoproteasome and the constitutive proteasome

et al. 2003

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Intracellular proteins are degraded largely by proteasomes. In cells stimulated with gamma interferon , the active proteasome subunits are replaced by "immuno" subunits that form immunoproteasomes. Phylogenetic analysis of the immunosubunits has revealed that they evolve faster than their constitutive counterparts. This suggests that the immunoproteasome has evolved a function that differs from that of the constitutive proteasome. Accumulating experimental degradation data demonstrate, indeed, that the specificity of the immunoproteasome and the constitutive proteasome differs. However, it has not yet been quantified how different the specificity of two forms of the proteasome are. The main question, which still lacks direct evidence, is whether the immunoproteasome generates more MHC ligands. Here we use bioinformatics tools to quantify these differences and show that the immunoproteasome is a more specific enzyme than the constitutive proteasome. Additionally, we predict the degradation of pathogen proteomes and find that the immunoproteasome generates peptides that are better ligands for MHC binding than peptides generated by the constitutive proteasome. Thus, our analysis provides evidence that the immunoproteasome has co-evolved with the major histocompatibility complex to optimize antigen presentation in vertebrate cells.

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“…Different cells can express different ratios of constitutive and immunoproteasome subunits (9,10). Variations in proteasomal composition affect substrate specificity and sensitivity to proteasome inhibition.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence-Based Proteasome Activity Profiling

Jong

Schuurman

Rodenko

et al. 2011

Methods in Molecular Biology

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The proteasome is a large protease complex responsible for the degradation of key regulatory proteins involved in many cellular processes, including cell proliferation and survival. The observation that cancer cells are more sensitive to proteasome inhibition than normal cells has led to the development of several proteasome inhibitors for the treatment of cancer. The proteasome inhibitor bortezomib (the active ingredient of Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, while a number of second-generation proteasome inhibitors, which differ in their mode of inhibition and subunit specificity, are currently in clinical trials. With the proteasome emerging as a therapeutic target for cancer treatment, accurate tools for monitoring proteasome (inhibitor) activity are in demand. In this chapter, the synthesis and use of a fluorescent proteasome activity probe is described that allows for accurate profiling of proteasomal activity in cell lysates, intact cells and murine and patient material, with high sensitivity using SDS-PAGE. The probe allows for direct scanning of the gel for fluorescent emission of the distinct proteasomal subunits and circumvents the use of western-blot analysis. Due to its suitable biochemical and biophysical properties the fluorescent probe can also be used for confocal laser scanning microscopy and flow cytometry-based experiments.

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Different proteasome subtypes in a single tissue exhibit different enzymatic properties 1 1Edited by R. Huber

Cited by 186 publications

References 34 publications

The proteasome and its role in the degradation of oxidized proteins

The proteasome and its role in the degradation of oxidized proteins

Bioinformatic analysis of functional differences between the immunoproteasome and the constitutive proteasome

Fluorescence-Based Proteasome Activity Profiling

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