Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases

Xiaoying Zhang; Yu'e Liu; Tong Zhang; Yuying Tan; Xiangpeng Dai; Yong-Guang Yang; Xiaoling Zhang

doi:10.3389/fimmu.2023.1125224

Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases

Front Immunol. 2023 Mar 17:14:1125224. doi: 10.3389/fimmu.2023.1125224. eCollection 2023.

Authors

Xiaoying Zhang^{1

2}, Yu'e Liu³, Tong Zhang^{1

2}, Yuying Tan^{1

2}, Xiangpeng Dai^{1

2}, Yong-Guang Yang^{1

2

4}, Xiaoling Zhang^{1

2}

Affiliations

¹ Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.
² National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital, Jilin University, Changchun, China.
³ Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, China.
⁴ International Center of Future Science, Jilin University, Changchun, China.

Abstract

Cullin-RING ligases (CRLs) are the largest class of E3 ubiquitin ligases regulating the stability and subsequent activity of a large number of important proteins responsible for the development and progression of various diseases, including autoimmune diseases (AIDs). However, the detailed mechanisms of the pathogenesis of AIDs are complicated and involve multiple signaling pathways. An in-depth understanding of the underlying regulatory mechanisms of the initiation and progression of AIDs will aid in the development of effective therapeutic strategies. CRLs play critical roles in regulating AIDs, partially by affecting the key inflammation-associated pathways such as NF-κB, JAK/STAT, and TGF-β. In this review, we summarize and discuss the potential roles of CRLs in the inflammatory signaling pathways and pathogenesis of AIDs. Furthermore, advances in the development of novel therapeutic strategies for AIDs through targeting CRLs are also highlighted.

Keywords: Cullin-RING ligases; E3 ligases; autoimmune diseases; inflammation; ubiquitination.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Autoimmune Diseases*
Cullin Proteins* / metabolism
Humans
Signal Transduction
Ubiquitin-Protein Ligases / metabolism
Ubiquitination

Substances

Cullin Proteins
Ubiquitin-Protein Ligases

Grants and funding

This work was partly supported by the National Key R&D Program of China (2021YFA1100700); a grant from the Department of Human Resource and Social Security of Jilin Province (2022DJ02) and Bethune Medical Department of Jilin University (2022JBGS01); the National Natural Science Foundation of China (No: 81972558 and No: 81802815); the “Startup Funding of First Hospital, JLU”; and the Natural Science Foundation of Jilin Province (No: 20200201367JC, No: 20210204165YY, and No: 20200201473JC).