A Destiny for Degradation: Interplay between Cullin-RING E3 Ligases and Autophagy. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: Lu, Guang; Wang, Liming; Zhou, Jing; Liu, Wei; Shen, Han-Ming
• Is Part Of: Trends in cell biology. Volume 31:Issue 6(2021)
• Page Start: 432
• Page End: 444
• Publication Date: 2021-06
• Subjects: autophagy -- cullin-RING E3 ligases -- ubiquitination -- neddylation -- MTORC1 -- cancer; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2021.01.005
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Autophagy and the ubiquitin-proteasome system (UPS) are two major pathways for protein degradation. The cullin-RING E3 ligases (CRLs) are the largest E3 ligase family and have key biological functions in maintaining protein homeostasis. We provide an updated review of the interactions between CRLs and autophagy, focusing on the regulatory effects of CRLs on the core autophagy machinery that consists of several autophagy-related protein (ATG) complexes and their key upstream signaling pathways. The involvement of such functional interactions in health and disease is also discussed. Understanding the role of CRLs in autophagy is helpful for the development of therapeutic strategies for diseases in which CRLs and autophagy are dysregulated, such as cancer and neurodegenerative conditions. Highlights: Autophagy is a highly conserved catabolic process that depends on autophagosome fusion with lysosomes for degradation. CRLs are the largest subfamily of RING E3 ligases and are responsible for ~20% of total protein degradation via the UPS. CRLs have emerged as crucial regulators of autophagy by targeting ATGs and upstream regulators such as MTORC1. Dysregulation of CRLs and autophagy is associated with human diseases such as cancer, neurodegenerative conditions, and cardiomyopathies.