Ubiquitin-proteasome system (UPS) as a target for anticancer treatment

被引:272
作者
Park, Jinyoung [1 ]
Cho, Jinhong [2 ]
Song, Eun Joo [2 ]
机构
[1] Korea Inst Sci & Technol, Mol Recognit Res Ctr, Hwarangno 14 Gil 5, Seoul 02792, South Korea
[2] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, 52 Ewhayeodae Gil, Seoul 03760, South Korea
基金
新加坡国家研究基金会;
关键词
Ubiquitin– proteasome system (UPS); E3; ligase; Deubiquitinating enzymes (DUBs); Proteasome; Cancer; Small molecule inhibitors; MULTIPLE-MYELOMA CELLS; CANCER THERAPEUTIC TARGET; SMALL-MOLECULE INHIBITOR; TUMOR-SUPPRESSOR CYLD; FATTY-ACID SYNTHASE; NF-KAPPA-B; BREAST-CANCER; IN-VIVO; PROMOTES PROLIFERATION; CYCLIN-E;
D O I
10.1007/s12272-020-01281-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:1144 / 1161
页数:18
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