Cullin-RING Ligase 5: Functional characterization and its role in human cancers.

Abstract

Cullin-RING ligase 5 (CRL5) is a multi-protein complex and consists of a scaffold protien cullin 5, a RING protein RBX2 (also known as ROC2 or SAG), adaptor proteins Elongin B/C, and a substrate receptor protein SOCS. Through targeting a variety of substrates for proteasomal degradation or modulating various protein-protein interactions, CRL5 is involved in regulation of many biological processes, such as cytokine signal transduction, inflammation, viral infection, and oncogenesis. As many substrates of CRL5 are well-known oncoproteins or tumor suppressors, abnormal regulation of CRL5 is commonly found in human cancers. In this review, we first briefly introduce each of CRL5 components, and then discuss the biological processes regulated by four members of SOCS-box-containing substrate receptor family through substrate degradation. We next describe how CRL5 is hijacked by a variety of viral proteins to degrade host anti-viral proteins, which facilitates virus infection. We further discuss the regulation of CUL5 and its various roles in human cancers, acting as either a tumor suppressor or an oncoprotein in a context-dependent manner. Finally, we propose novel insights for future perspectives on the validation of cullin5 and other CRL5 components as potential targets, and possible targeting strategies to discover CRL5 inhibitors for anti-cancer and anti-virus therapies.

• Authors: Yongchao Zhao, Xiufang Xiong, Yi Sun
• Journal: Seminars in cancer biology (Semin Cancer Biol) Vol. 67 Issue Pt 2 Pg. 61-79 (12 2020) ISSN: 1096-3650 [Electronic] England
• PMID: 32334051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antiviral Agents
• CUL5 protein, human
• Carrier Proteins
• Cullin Proteins
• Multiprotein Complexes
• RBX1 protein, human
• Suppressor of Cytokine Signaling Proteins
• Viral Proteins
• RNF7 protein, human
• Ubiquitin-Protein Ligases

Topics

• Antiviral Agents (pharmacology)
• Carrier Proteins (metabolism)
• Cullin Proteins (genetics, metabolism)
• Humans
• Molecular Targeted Therapy (methods)
• Multiprotein Complexes (metabolism)
• Neoplasms (genetics, metabolism)
• Suppressor of Cytokine Signaling Proteins (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Viral Proteins (metabolism)