The Immunoproteasome: An Emerging Target in Cancer and Autoimmune and Neurological Disorders.
| Autor: | Zerfas BL; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, Indiana 47907, United States., Maresh ME; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, Indiana 47907, United States., Trader DJ; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 West Stadium Avenue, West Lafayette, Indiana 47907, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of medicinal chemistry [J Med Chem] 2020 Mar 12; Vol. 63 (5), pp. 1841-1858. Date of Electronic Publication: 2019 Nov 21. |
| DOI: | 10.1021/acs.jmedchem.9b01226 |
| Abstrakt: | The immunoproteasome (iCP) is an isoform of the 20S proteasome that is expressed when cells are stressed or receive an inflammatory signal. The primary role of the iCP is to hydrolyze proteins into peptides that are compatible with being loaded into a MHC-I complex. When the activity of the iCP is dysregulated or highly expressed, it can lead to unwanted cell death. Some cancer types express the iCP rather than the standard proteasome, and selective inhibitors have been developed to exploit this difference. Here, we describe diseases known to be influenced by iCP activity and the current status for targeting the iCP to elicit a therapeutic response. We also describe a variety of chemical tools that have been developed to monitor the activity of the iCP in cells. Finally, we present the future outlook for targeting the iCP in a variety of disease types and with mechanisms besides inhibition. |
| Databáze: | MEDLINE |
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