期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 63, 期 5, 页码 1841-1858出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.9b01226
关键词
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资金
- Purdue University School of Pharmacy
- Purdue University Center for Cancer Research National Institutes of Health (NIH) Grant [P30 CA023168]
- American Cancer Society Institutional Research Grant [IRG-14-190-56]
- NIH [R21GM131206]
- Purdue University Center for Cancer Research
- Showalter Research Trust Grant
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.
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