Journal
ARCHIVES OF PHARMACAL RESEARCH
Volume 43, Issue 11, Pages 1144-1161Publisher
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-020-01281-8
Keywords
Ubiquitin– proteasome system (UPS); E3 ligase; Deubiquitinating enzymes (DUBs); Proteasome; Cancer; Small molecule inhibitors
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Funding
- National Research Foundation of Korea (NRF) - Korean government (MSIP) [2020R1A4A4079494, 2019R1A2C2004052]
- National Research Foundation of Korea [2019R1A2C2004052, 2020R1A4A4079494] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The ubiquitin-proteasome system (UPS) plays an important role in the cellular processes for protein quality control and homeostasis. Dysregulation of the UPS has been implicated in numerous diseases, including cancer. Indeed, components of UPS are frequently mutated or abnormally expressed in various cancers. Since Bortezomib, a proteasome inhibitor, received FDA approval for the treatment of multiple myeloma and mantle cell lymphoma, increasing numbers of researchers have been seeking drugs targeting the UPS as a cancer therapeutic strategy. Here, we introduce the essential component of UPS, including ubiquitinating enzymes, deubiquitinating enzymes and 26S proteasome, and we summarize their targets and mechanisms that are crucial for tumorigenesis. In addition, we briefly discuss some UPS inhibitors, which are currently in clinical trials as cancer therapeutics.
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