Genomes and Genes
Affiliation: Humboldt University
- Antigen processing by the proteasomeP M Kloetzel
Institut fur Biochemie, Medical Faculty, Charite, Humboldt University, Monbijoustrasse 2, 10117 Berlin, Germany
Nat Rev Mol Cell Biol 2:179-87. 2001..But proteasomes--the waste-disposal units of the cell--typically do not generate peptides for antigen presentation with high efficiency. How, then, does the proteasome adapt to serve the immune system well?..
- The FAT10- and ubiquitin-dependent degradation machineries exhibit common and distinct requirements for MHC class I antigen presentationFrederic Ebstein
Institut fur Biochemie, Charite Universitatsmedizin Berlin, Campus CVK, Germany
Cell Mol Life Sci 69:2443-54. 2012..Collectively, our data establish FAT10 modification as a distinct and alternative signal for facilitated MHC class I antigen presentation...
- The role of the proteasome in the generation of MHC class I ligands and immune responsesE J A M Sijts
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands
Cell Mol Life Sci 68:1491-502. 2011..We further discuss recently discovered functions of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses...
- The proteasome and MHC class I antigen processingPeter M Kloetzel
Institut fur Biochemie, Charite, Medizinische Fakultat der Humboldt Universitat zu Berlin, Monbijoust 2, 10117 Berlin, Germany
Biochim Biophys Acta 1695:225-33. 2004..Thus, a combination of several of regulatory events tunes the proteasome system for maximal efficiency in the generation of MHC class I antigens...
- Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPIIPeter M Kloetzel
Institut fur Biochemie, University Medical School Charité, Humboldt Universität Monbijoustr 2, 10117 Berlin, Germany
Nat Immunol 5:661-9. 2004..We therefore revisit the interferon-gamma-induced immune adaptation of the proteasome and attempt to redefine its function in connection with the emerging importance of TPPII...
- Proteasome and peptidase function in MHC-class-I-mediated antigen presentationPeter Michael Kloetzel
Institut fur Biochemie, Charité Medizinische Fakultät der Humboldt Universität zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
Curr Opin Immunol 16:76-81. 2004..Recent evidence suggests that tripeptidyl peptidase II (TPPII), a large peptidase with exo-and endo-proteolytic activities, is also involved in antigen processing and may generate a specific set of MHC class I epitopes...
- Tumor cell lines expressing the proteasome subunit isoform LMP7E1 exhibit immunoproteasome deficiencySylvia Heink
Institute of Biochemistry, Charité Universitätsmedizin Berlin CCM, Monbijoustrasse 2, 10117 Berlin, Germany
Cancer Res 66:649-52. 2006..However, expression of LMP7E2 in these cells restores the i20S-deficient phenotype. Thus, our data describe a novel mechanism that contributes to the process of oncogenesis...
- IFN-gamma-induced immune adaptation of the proteasome system is an accelerated and transient responseSylvia Heink
Institute of Biochemistry, Charite Universitatsmedizin Berlin, 10117 Berlin, Germany
Proc Natl Acad Sci U S A 102:9241-6. 2005....
- A role for the proteasome regulator PA28alpha in antigen presentationM Groettrup
Institute for Biochemistry, Medical Faculty Charité, Humboldt University, Berlin, Germany
Nature 381:166-8. 1996..These results demonstrate a fundamental in vivo function for PA28alpha in antigen processing...
- PI31 is a modulator of proteasome formation and antigen processingDietmar M W Zaiss
Institute of Biochemistry, Medical Faculty Charité, Humboldt University, D 10117 Berlin, Germany
Proc Natl Acad Sci U S A 99:14344-9. 2002..Thus, PI31 represents a cellular regulator of proteasome formation and of proteasome-mediated antigen processing...
- The role of the proteasome activator PA28 in MHC class I antigen processingAlice Sijts
Institut fur Biochemie, Charité Medizinische Fakültät der, Humboldt Universitat zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
Mol Immunol 39:165-9. 2002..Our results show that PA28 selectively up-regulates the presentation of viral MHC class I epitopes and that down regulation PA28 in tumor cells results in impaired presentation of a human TRP2 tumor antigen...
- Hepatitis C virus mutation affects proteasomal epitope processingUlrike Seifert
Institute of Biochemistry, Charit, Humboldt University, Berlin, Germany
J Clin Invest 114:250-9. 2004....
- The murine cytomegalovirus pp89 immunodominant H-2Ld epitope is generated and translocated into the endoplasmic reticulum as an 11-mer precursor peptideC Knuehl
Institute of Biochemistry, Medical Faculty, , Humboldt University, Monbijoustrasse 2a, 10117 Berlin, Germany
J Immunol 167:1515-21. 2001..In consequence, our combined proteasome/TAP assays show that the 11-mer precursor is the immunorelevant peptide product that requires N-terminal trimming in the ER for MHC class I binding...
- Combined effect of proteasome and calpain inhibition on cisplatin-resistant human melanoma cellsIzabela Młynarczuk-Biały
Institut fuer Biochemie, Charite Universitaetsmedizin Berlin, Monbijoustrasse 2, 10117 Berlin, Germany
Cancer Res 66:7598-605. 2006..Thus, combined strategies targeting distinct proteolytic pathways may help to overcome mechanisms of drug resistance in tumor cells...
- Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal alpha and beta subunitsG Sébastien Apcher
Humboldt Universitat zu Berlin, Universitatsklinikum Charite, Institut fur Biochemie, Germany
FEBS Lett 553:200-4. 2003..This indicates that Tat can modulate or interfere with cellular proteasome function by specific interaction with distinct proteasomal subunits...
- An essential role for tripeptidyl peptidase in the generation of an MHC class I epitopeUlrike Seifert
, Medical Faculty of the Humboldt-University Berlin, Monbijoustr. 2, 10117 Berlin, Germany
Nat Immunol 4:375-9. 2003..We propose that TPPII can act in combination with or independent of the proteasome system and can generate epitopes that evade generation by the proteasome-system...
- Circulating proteasome levels are an independent prognostic factor for survival in multiple myelomaChristian Jakob
Department of Hematology and Oncology, Charite Universitatsmedizin Berlin, Germany
Blood 109:2100-5. 2007..38) survival analysis in patients with active MM. We demonstrate for the first time that increased serum proteasome concentrations correlate with advanced disease and are an independent prognostic factor in MM...
- Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseasesKarl Egerer
Department of Rheumatology and Clinical Immunology, Institute of Biochemistry, Humboldt University of Berlin, Berlin, Germany
J Rheumatol 29:2045-52. 2002..The cProteasomes represent novel sensitive markers of the autoimmune inflammatory processes and/or reflect the magnitude of cellular damage...
- Sequence information within proteasomal prosequences mediates efficient integration of beta-subunits into the 20 S proteasome complexM Schmidt
Institut fur Biochemie, Medizinische Fakultät der Humboldt Universität zu Berlin Charité, Monbijoustr 2, Berlin, 10117, Germany
J Mol Biol 288:117-28. 1999..The contribution of beta5i/LMP7 on the cooperative formation of a homogeneous population of immunoproteasome is therefore most likely based on an acceleration of the beta1i/LMP2 and potentially of beta2i/MECL1 processing kinetics...
- Characterisation of the newly identified human Ump1 homologue POMP and analysis of LMP7(beta 5i) incorporation into 20 S proteasomesE Witt
Institut fur Biochemie, Charité Humboldt University Medical School, Monbijoustr 2, Berlin, 10117, Germany
J Mol Biol 301:1-9. 2000..As a result of the precursor accumulation, an increased amount of the POMP protein can be detected in these cells...
- Biochemical analysis of proteasomes from mouse microglia: induction of immunoproteasomes by interferon-gamma and lipopolysaccharideR Stohwasser
Paul Ehrlich Center of Experimental Medicine, Humboldt University Medical School, Institute of Biochemistry, Berlin, Germany
Glia 29:355-65. 2000..These results indicate that both the 20S core protease as well as the proteasome activator PA700 are targets of modulatory subunit replacements or transient association of regulatory components in the course of microglial activation...
- A kinetic model of vertebrate 20S proteasome accounting for the generation of major proteolytic fragments from oligomeric peptide substratesH G Holzhutter
Humboldt Universitat zu Berlin, Medizinische Fakultät Charité, Institut fur Biochemie, D 10117 Berlin, Germany
Biophys J 79:1196-205. 2000..This finding strongly supports the idea that generation of fragments with well-defined lengths is favored in that temporary immobilization of the downstream fragment after the first cleavage renders it susceptible for a second cleavage...
- Different proteasome subtypes in a single tissue exhibit different enzymatic propertiesB Dahlmann
Department of Clinical Biochemistry, Deutsches Diabetes Forschungsinstitut, Dusseldorf, Germany
J Mol Biol 303:643-53. 2000..Therefore, the characteristics of proteasomes purified from tissues or cells represent the average of the different subtype activities which in turn may have different functions in vivo...
- PA28alphabeta double and PA28beta single transfectant mouse B8 cell lines reveal enhanced presentation of a mouse cytomegalovirus (MCMV) pp89 MHC class I epitopeR Stohwasser
Institute of Biochemistry, Medical Faculty Charité, Humboldt University, Monbijoustrasse 2, 10117, Berlin, Germany
Mol Immunol 37:13-9. 2000....
- Subtypes of 20S proteasomes from skeletal muscleB Dahlmann
Institut für Biochemie Charité, Humboldt Universitat Berlin, Monbijoustr 2, 10117, Berlin, Germany
Biochimie 83:295-9. 2001..Our data show that the properties of 20S proteasomes isolated from a given tissue or cells are always the average of the properties of the whole set of proteasome subtypes...
- The role of the ubiquitin-proteasome pathway in MHC class I antigen processing: implications for vaccine designA Sijts
Institute of Biochemistry, Charite Medical School, Humboldt University Berlin, Germany
Curr Mol Med 1:665-76. 2001..The availability of such programs as well as a general insight into the proteasome mediated steps in MHC class I antigen processing provides us with a rational basis for the design of new antiviral and anticancer T cell vaccines...
- Link between organ-specific antigen processing by 20S proteasomes and CD8(+) T cell-mediated autoimmunityUlrike Kuckelkorn
Institute of Biochemistry, Charite, Humboldt University, D-10117 Berlin, Germany
J Exp Med 195:983-90. 2002..We propose tissue-specific antigen processing by 20S proteasomes as a potential mechanism to control organ-specific immune responses...
- Molecular cloning of the mouse proteasome subunits MC14 and MECL-1: reciprocally regulated tissue expression of interferon-gamma-modulated proteasome subunitsR Stohwasser
Institute for Biochemistry, Medical Faculty Charité, Humboldt University, Berlin, Germany
Eur J Immunol 27:1182-7. 1997..The impact of a regulated reciprocal tissue expression is discussed with respect to thymic selection and the induction of tolerance in potentially autoreactive T cells...
- 20S proteasome biogenesisE Kruger
Institut fur Biochemie, Humboldt Universitat zu Berlin, Universitatsklinikum Charite, Monbijoustr 2, 10117, Berlin, Germany
Biochimie 83:289-93. 2001..The major localization of yeast proteasomes may point to the subcellular place of proteasome biogenesis...
- Functional analysis of eukaryotic 20S proteasome nuclear localization signalC Knuehl
Institut fur Biochemie, Charite, Hunboldt Universitat zu Berlin, Federal Republic of Germany
Exp Cell Res 225:67-74. 1996..Whereas the deletion of the NLS alone resulted only in a slight impairment of subunit transport into the nucleus, removal of the C-terminal 96 amino acid residues abolished nuclear translocation completely...
- Analysis of mammalian 20S proteasome biogenesis: the maturation of beta-subunits is an ordered two-step mechanism involving autocatalysisG Schmidtke
Institut fur Biochemie, Charite, Humboldt Universitat zu Berlin, Germany
EMBO J 15:6887-98. 1996..We provide evidence that subunit processing of mammalian beta-subunits proceeds via a novel ordered two-step mechanism involving autocatalysis...
- Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of Mammalian proteasomesSilke Meiners
, , , Monbijoustrasse 2, 10117 Berlin, Germany
J Biol Chem 278:21517-25. 2003....
- A second gene encoding the mouse proteasome activator PA28beta subunit is part of a LINE1 element and is driven by a LINE1 promoterD M Zaiss
Institute of Biochemistry Charité, Humboldt University Medical School, Humboldt University, Monbijoustrasse 2, Berlin, 10117, Germany
J Mol Biol 287:829-35. 1999....
- Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeastC Enenkel
Institut fur Biochemie, Humboldt Universitat, Universitatsklinikum Charite, Monbijoustrasse 2, D 10117 Berlin, Germany
EMBO J 17:6144-54. 1998..A major location of proteasomal peptide cleavage activity was visualized in the NE-ER network, indicating that proteasomal degradation takes place mainly in this subcellular compartment in yeast...
- The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processingXiaohua Huang
Division of Molecular Biology, Department of Surgery, Medical Faculty Charit, Humboldt University, Monbijoustr. 2A, Berlin, Germany
J Mol Biol 323:771-82. 2002..In contrast, the Tat peptide 37-72 with mutations of amino acid residues Lys51, Arg52 and Asp67 to Ala was not able to reduce antigen presentation...
- A comprehensive view on proteasomal sequences: implications for the evolution of the proteasomeChristoph Gille
Institute of Biochemistry, Medical Faculty Charité, Humboldt University, D 10117, Berlin, Germany
J Mol Biol 326:1437-48. 2003..The structure-based multiple proteasomal alignment of 433 sequences from 143 organisms can be downloaded from the URL dagger and will be updated regularly...