Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes - PubMed (original) (raw)
. 1993 Sep 16;365(6443):264-7.
doi: 10.1038/365264a0.
Affiliations
- PMID: 8396732
- DOI: 10.1038/365264a0
Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes
M Gaczynska et al. Nature. 1993.
Erratum in
- Nature 1995 Mar 16;374(6519):290
Abstract
The presentation of intracellular proteins to the immune system requires their degradation to small peptides that then become associated with major histocompatibility complex (MHC) class I molecules. The generation of these peptides may involve the 20S or 26S proteasome particles, which contain multiple proteolytic activities including distinct sites that preferentially cleave small peptides on the carboxyl side of hydrophobic, basic or acidic residues. Degradation of most cell proteins requires their conjugation to ubiquitin before hydrolysis by the 26S proteasome. This large complex contains the 20S proteasome as its proteolytic core. This ubiquitin-dependent proteolytic pathway is implicated in MHC class I presentation. gamma-Interferon (gamma-IFN), a stimulator of antigen presentation, induces a subclass of proteasomes that contain two MHC-encoded subunits, LMP2 and 7 (refs 5-10). Here we show that gamma-interferon alters the peptidase activities of the 20S and 26S proteasomes without affecting the rates of breakdown of proteins or of ubiquitinated proteins. By enhancing the expression of MHC genes, gamma-IFN increases the proteasomes' capacity to cleave small peptides after hydrophobic and basic residues but reduces cleavage after acidic residues. Moreover, proteasomes of mutants lacking LMP subunits show decreased rates of cleavage after hydrophobic and basic residues. Thus, gamma-IFN and expression of these MHC genes should favour the production by proteasomes of the types of peptides found on MHC class I molecules, which terminate almost exclusively with hydrophobic or basic residues.
Comment in
- Antigen processing. Peptides and the proteasome.
Howard JC, Seelig A. Howard JC, et al. Nature. 1993 Sep 16;365(6443):211-2. doi: 10.1038/365211a0. Nature. 1993. PMID: 8371776 No abstract available.
Similar articles
- MHC-linked LMP gene products specifically alter peptidase activities of the proteasome.
Driscoll J, Brown MG, Finley D, Monaco JJ. Driscoll J, et al. Nature. 1993 Sep 16;365(6443):262-4. doi: 10.1038/365262a0. Nature. 1993. PMID: 8371781 - MHC-encoded proteasome subunits LMP2 and LMP7 are not required for efficient antigen presentation.
Yewdell J, Lapham C, Bacik I, Spies T, Bennink J. Yewdell J, et al. J Immunol. 1994 Feb 1;152(3):1163-70. J Immunol. 1994. PMID: 8301122 - Incorporation of major histocompatibility complex--encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon-gamma.
Kuckelkorn U, Frentzel S, Kraft R, Kostka S, Groettrup M, Kloetzel PM. Kuckelkorn U, et al. Eur J Immunol. 1995 Sep;25(9):2605-11. doi: 10.1002/eji.1830250930. Eur J Immunol. 1995. PMID: 7589133 - Role of proteasomes in antigen presentation.
Gaczynska M, Rock KL, Goldberg AL. Gaczynska M, et al. Enzyme Protein. 1993;47(4-6):354-69. doi: 10.1159/000468693. Enzyme Protein. 1993. PMID: 7697133 Review. - Interferon-gamma, the functional plasticity of the ubiquitin-proteasome system, and MHC class I antigen processing.
Strehl B, Seifert U, Krüger E, Heink S, Kuckelkorn U, Kloetzel PM. Strehl B, et al. Immunol Rev. 2005 Oct;207:19-30. doi: 10.1111/j.0105-2896.2005.00308.x. Immunol Rev. 2005. PMID: 16181324 Review.
Cited by
- Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins.
Abi Habib J, De Plaen E, Stroobant V, Zivkovic D, Bousquet MP, Guillaume B, Wahni K, Messens J, Busse A, Vigneron N, Van den Eynde BJ. Abi Habib J, et al. Sci Rep. 2020 Sep 25;10(1):15765. doi: 10.1038/s41598-020-71550-5. Sci Rep. 2020. PMID: 32978409 Free PMC article. - The immunoproteasome as a target in hematologic malignancies.
Kuhn DJ, Orlowski RZ. Kuhn DJ, et al. Semin Hematol. 2012 Jul;49(3):258-62. doi: 10.1053/j.seminhematol.2012.04.003. Semin Hematol. 2012. PMID: 22726549 Free PMC article. Review. - Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer.
Li X, Ruan Z, Yang S, Yang Q, Li J, Hu M. Li X, et al. Int J Mol Sci. 2024 Sep 30;25(19):10546. doi: 10.3390/ijms251910546. Int J Mol Sci. 2024. PMID: 39408874 Free PMC article. - Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma.
Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kanai Y, Shiozawa T, Tonegawa S, Konishi I. Hayashi T, et al. Protein Cell. 2010 Aug;1(8):711-7. doi: 10.1007/s13238-010-0095-x. Epub 2010 Aug 28. Protein Cell. 2010. PMID: 21203912 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials