Killing by degradation: Regulation of apoptosis by the ubiquitin-proteasome-system

Ruqaia Abbas, Sarit Larisch

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis is a cell suicide process that is essential for development, tissue homeostasis and human health. Impaired apoptosis is associated with a variety of human diseases, including neurodegenerative disorders, autoimmunity and cancer. As the levels of pro-and anti-apoptotic proteins can determine the life or death of cells, tight regulation of these proteins is critical. The ubiquitin proteasome system (UPS) is essential for maintaining protein turnover, which can either trigger or inhibit apoptosis. In this review, we will describe the E3 ligases that regulate the levels of pro-and anti-apoptotic proteins and assisting proteins that regulate the levels of these E3 ligases. We will provide examples of apoptotic cell death modulations using the UPS, determined by positive and negative feedback loop reactions. Specifically, we will review how the stability of p53, Bcl-2 family members and IAPs (Inhibitor of Apoptosis proteins) are regulated upon initiation of apoptosis. As increased levels of oncogenes and decreased levels of tumor suppressor proteins can promote tumorigenesis, targeting these pathways offers opportunities to develop novel anti-cancer therapies, which act by recruiting the UPS for the effective and selective killing of cancer cells.

Original languageEnglish
Article number3465
JournalCells
Volume10
Issue number12
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by U.S. Israel Binational Science Foundation Grant 2003085, Israel Science Foundation (ISF) Grants 1264/06 and 822/12, INCPM-ISF Grant 2376/15, by the Charles Wolfson Charitable Trust and by a generous grant award from the Hymen Milgrom Trust.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • ARTS
  • Bcl-2
  • CIAP
  • MDM2
  • Mcl-1
  • P53
  • Parkin
  • Smac
  • Ubiquitin proteasome system
  • XIAP

ASJC Scopus subject areas

  • Medicine (all)

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