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Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System

Laboratory of Cell Death and Cancer Research, Biology & Human Biology Departments, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel
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Academic Editor: Amir Orian
Cells 2021, 10(12), 3465; https://doi.org/10.3390/cells10123465
Received: 9 November 2021 / Revised: 2 December 2021 / Accepted: 3 December 2021 / Published: 8 December 2021
(This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Pathways in Development and Disease)
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. View Full-Text
Keywords: ubiquitin proteasome system; ARTS; Smac; XIAP; cIAP; Bcl-2; Mcl-1; parkin; p53; MDM2 ubiquitin proteasome system; ARTS; Smac; XIAP; cIAP; Bcl-2; Mcl-1; parkin; p53; MDM2
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MDPI and ACS Style

Abbas, R.; Larisch, S. Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System. Cells 2021, 10, 3465. https://doi.org/10.3390/cells10123465

AMA Style

Abbas R, Larisch S. Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System. Cells. 2021; 10(12):3465. https://doi.org/10.3390/cells10123465

Chicago/Turabian Style

Abbas, Ruqaia, and Sarit Larisch. 2021. "Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System" Cells 10, no. 12: 3465. https://doi.org/10.3390/cells10123465

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