Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7
Open accessAbstract
Recent studies have implicated proteasomes in the generation of the antigenic peptides that are presented on major histocompatibility complex class I molecules to T lymphocytes. Interferon gamma modifies the subunit composition of proteasomes and causes changes in their peptidase activities that should favor the production of peptides with hydrophobic or basic carboxyl termini (i.e., the types found on major histocompatibility complex class I molecules). It has been proposed that these changes in peptidase activity are due to incorporation into proteasomes of the major histocompatibility complex-encoded subunits LMP2 and -7, which are induced by interferon gamma. Here we show by gene transfection into lymphoblasts or HeLa cells that LMP7 increases the capacity (Vmax) of 20S and 26S proteasomes to cleave peptides after hydrophobic and basic residues without affecting hydrolysis after acidic residues. These changes depended on the amount of LMP7 subunits incorporated into proteasomes. Transfection of LMP2 reduced cleavage of peptides after acidic residues, increased hydrolysis after basic residues, and did not affect the hydrophobic activity. Since the activity of the total proteasome population changed after incorporation of only small amounts of LMP2 or -7, these subunits must cause major alterations in peptidase activity. Thus, their expression can account for the changes in proteasome activity induced by inteferon gamma, and these findings lend further support to the proposed roles of LMPs in altering the nature of the peptides generated for antigen presentation.
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Cytokines such as IL-6 and TNFα stimulate muscle breakdown, producing amino acids for energy and releasing antigenic peptides.
“Inflammatory cytokines including IL-6 and TNFα activate muscle breakdown to generate amino acids for energy and cleave antigenic peptides (69).”
From Frailty in elderly people (2013) · cites this paper as [69]
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- Authors
- Gaczynska, M., Rock, K. L., Spies, T., & Goldberg, A. L.
- Affiliations
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-09-27
- Volume
- 91
- Issue
- 20
- Pages
- 9213-9217
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44782
- OpenAlex
- W2092725115
- Cited by
- 312
- References
- 32
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 4 · 2014: 14 · 2013: 12 · 2012: 16
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- Muscular Dystrophy Association
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM046147, GM-46147)
- National Institute of Allergy and Infectious Diseases (AI-20248)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- proteasome, LMP2, LMP7, MHC class I antigen presentation, proteolytic activity, interferon-gamma, 20S proteasome, 26S proteasome, antigen processing
- MeSH terms
- Amino Acid Sequence, B-Lymphocytes, Cell Line, Cysteine Endopeptidases, HeLa Cells, Humans, Interferon-gamma, Kinetics, Major Histocompatibility Complex, Molecular Sequence Data, Multienzyme Complexes, Oligopeptides, Endopeptidases, Proteins, Substrate Specificity, T-Lymphocytes, Transfection, Protein Biosynthesis, Gene Expression Regulation, Enzymologic, Proteasome Endopeptidase Complex
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