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ARID3a from the ARID family: structure, role in autoimmune diseases and drug discovery

Acta Pharmacologica Sinica volume 44, pages 2139–2150 (2023)Cite this article

Abstract

The AT-rich interaction domain (ARID) family of DNA-binding proteins is a group of transcription factors and chromatin regulators with a highly conserved ARID domain that recognizes specific AT-rich DNA sequences. Dysfunction of ARID family members has been implicated in various human diseases including cancers and intellectual disability. Among them, ARID3a has gained increasing attention due to its potential involvement in autoimmunity. In this article we provide an overview of the ARID family, focusing on the structure and biological functions of ARID3a. It explores the role of ARID3a in autoreactive B cells and its contribution to autoimmune diseases such as systemic lupus erythematosus and primary biliary cholangitis. Furthermore, we also discuss the potential for drug discovery targeting ARID3a and present a plan for future research in this field.

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Fig. 1: The human ARID family, which is classified into seven subfamilies, ARID1-5 and JARID1-2, based on the sequence homology of the shared ARID domain.
Fig. 2: Sequence alignment of the ARID domain of ARID proteins with known structures.
Fig. 3: ARID-DNA complexes.
Fig. 4: ARID3a plays a role in gene regulation.
Fig. 5: ARID3a and autoreactive B cells.
Fig. 6: ARID3a and SLE.

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Acknowledgements

This work was partially supported by Ministry of Science and Technology (China) grants (2018YFA0507002 to HEX); Shanghai Municipal Science and Technology Major Project (2019SHZDZX02 to HEX); Shanghai Municipal Science and Technology Major Project (HEX); CAS Strategic Priority Research Program (XDB37030103 to HEX); the National Natural Science Foundation of China (32130022 and 82121005 to HEX, 81830016, 81771732 and 81620108002 to XM). We have used chatGPT to help the authors correct language and grammatic errors.

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  1. Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, 200001, China

    Cheng-cen Guo & Xiong Ma

  2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    H. Eric Xu

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    H. Eric Xu

  4. School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China

    H. Eric Xu

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  1. Cheng-cen Guo
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Correspondence to Cheng-cen Guo, H. Eric Xu or Xiong Ma.

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HEX is the founder and chairman of board of Cascade Pharmaceutics. CCG and XM do not have conflicts of interest to declare.

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Guo, Cc., Xu, H.E. & Ma, X. ARID3a from the ARID family: structure, role in autoimmune diseases and drug discovery. Acta Pharmacol Sin 44, 2139–2150 (2023). https://doi.org/10.1038/s41401-023-01134-2

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