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

Jinyoung Park, Jinhong Cho, Eun Joo Song

Research output: Contribution to journalReview articlepeer-review

167 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1144-1161
Number of pages18
JournalArchives of Pharmacal Research
Volume43
Issue number11
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2020R1A4A4079494 and 2019R1A2C2004052).

Publisher Copyright:
© 2020, The Pharmaceutical Society of Korea.

Keywords

  • Cancer
  • Deubiquitinating enzymes (DUBs)
  • E3 ligase
  • Proteasome
  • Small molecule inhibitors
  • Ubiquitin–proteasome system (UPS)

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