The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer
Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3587 |
| _version_ | 1797505912682840064 |
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| author | Satyendra Chandra Tripathi Disha Vedpathak Edwin Justin Ostrin |
| author_facet | Satyendra Chandra Tripathi Disha Vedpathak Edwin Justin Ostrin |
| author_sort | Satyendra Chandra Tripathi |
| collection | DOAJ |
| description | Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. While accelerated proteasomal degradation is an important tumorigenic mechanism deployed by several cancers, there is some ambiguity regarding the role of immunoproteasome induction in neoplastic transformation. Understanding the mechanistic and functional relevance of the immunoproteasome provides essential insights into developing targeted therapies, including overcoming resistance to standard proteasome inhibition and immunomodulation of the tumor microenvironment. In this review, we discuss the roles of the immunoproteasome in different cancers. |
| first_indexed | 2024-03-10T04:25:06Z |
| format | Article |
| id | doaj.art-bb4d2204e374493b9cb772f06bc197f1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:25:06Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bb4d2204e374493b9cb772f06bc197f12023-11-23T07:39:52ZengMDPI AGCells2073-44092021-12-011012358710.3390/cells10123587The Functional and Mechanistic Roles of Immunoproteasome Subunits in CancerSatyendra Chandra Tripathi0Disha Vedpathak1Edwin Justin Ostrin2Department of Biochemistry, All India Institute of Medical Sciences Nagpur, Nagpur 441108, MH, IndiaDepartment of Biochemistry, All India Institute of Medical Sciences Nagpur, Nagpur 441108, MH, IndiaDepartment of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USACell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. While accelerated proteasomal degradation is an important tumorigenic mechanism deployed by several cancers, there is some ambiguity regarding the role of immunoproteasome induction in neoplastic transformation. Understanding the mechanistic and functional relevance of the immunoproteasome provides essential insights into developing targeted therapies, including overcoming resistance to standard proteasome inhibition and immunomodulation of the tumor microenvironment. In this review, we discuss the roles of the immunoproteasome in different cancers.https://www.mdpi.com/2073-4409/10/12/3587ubiquitin–proteasome system (UPS)immunoproteasomesolid tumorsproteasome inhibitors |
| spellingShingle | Satyendra Chandra Tripathi Disha Vedpathak Edwin Justin Ostrin The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer Cells ubiquitin–proteasome system (UPS) immunoproteasome solid tumors proteasome inhibitors |
| title | The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer |
| title_full | The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer |
| title_fullStr | The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer |
| title_full_unstemmed | The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer |
| title_short | The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer |
| title_sort | functional and mechanistic roles of immunoproteasome subunits in cancer |
| topic | ubiquitin–proteasome system (UPS) immunoproteasome solid tumors proteasome inhibitors |
| url | https://www.mdpi.com/2073-4409/10/12/3587 |
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