Rack1 regulates B-cell development and function by binding to and stabilizing the transcription factor Pax5.

Autor: Zhang X; Beijing Institute of Basic Medical Sciences, Beijing, China., Ma C; Beijing Institute of Basic Medical Sciences, Beijing, China., Lu Y; Beijing Institute of Basic Medical Sciences, Beijing, China., Wang J; Beijing Institute of Basic Medical Sciences, Beijing, China., Yun H; Beijing Institute of Basic Medical Sciences, Beijing, China., Jiang H; Beijing Institute of Basic Medical Sciences, Beijing, China.; University of South China, Hengyang Medical School, Hengyang, China., Wu M; Beijing Institute of Basic Medical Sciences, Beijing, China.; Anhui Medical University, Hefei, China., Feng X; Beijing Institute of Basic Medical Sciences, Beijing, China.; Henan University Joint National Laboratory for Antibody Drug Engineering, Kaifeng, China., Gai W; Beijing Institute of Basic Medical Sciences, Beijing, China., Xu G; Beijing Institute of Basic Medical Sciences, Beijing, China., Deng H; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Feng J; Henan University Joint National Laboratory for Antibody Drug Engineering, Kaifeng, China.; National Engineering Research Center for Emergence Drugs, Beijing Institute of Pharmacology and Toxicology, Beijing, China., Liu W; Institute of Life Sciences, Tsinghua University, Beijing, China., Shi T; Beijing Institute of Basic Medical Sciences, Beijing, China. shitaoxing@sina.com., Cheng Q; Beijing Institute of Basic Medical Sciences, Beijing, China. chengqianqian044271@126.com., Zhang J; Beijing Institute of Basic Medical Sciences, Beijing, China. zhangjy@bmi.ac.cn.; University of South China, Hengyang Medical School, Hengyang, China. zhangjy@bmi.ac.cn.; Anhui Medical University, Hefei, China. zhangjy@bmi.ac.cn.; Henan University Joint National Laboratory for Antibody Drug Engineering, Kaifeng, China. zhangjy@bmi.ac.cn.; Chinese Institute for Brain Research, Beijing, China. zhangjy@bmi.ac.cn.
Jazyk: angličtina
Zdroj: Cellular & molecular immunology [Cell Mol Immunol] 2024 Nov; Vol. 21 (11), pp. 1282-1295. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1038/s41423-024-01213-2
Abstrakt: The transcription factor Pax5 activates genes essential for B-cell development and function. However, the regulation of Pax5 expression remains elusive. The adaptor Rack1 can interact with multiple transcription factors and modulate their activation and/or stability. However, its role in the transcriptional control of B-cell fates is largely unknown. Here, we show that CD19-driven Rack1 deficiency leads to pro-B accumulation and a simultaneous reduction in B cells at later developmental stages. The generation of bone marrow chimeras indicates a cell-intrinsic role of Rack1 in B-cell homeostasis. Moreover, Rack1 augments BCR and TLR signaling in mature B cells. On the basis of the aberrant expression of Pax5-regulated genes, including CD19, upon Rack1 deficiency, further exploration revealed that Rack1 maintains the protein level of Pax5 through direct interaction and consequently prevents Pax5 ubiquitination. Accordingly, Mb1-driven Rack1 deficiency almost completely blocks B-cell development at the pro-B-cell stage. Ectopic expression of Pax5 in Rack1-deficient pro-B cells partially rescues B-cell development. Thus, Rack1 regulates B-cell development and function through, at least partially, binding to and stabilizing Pax5.
(© 2024. The Author(s), under exclusive licence to CSI and USTC.)
Databáze: MEDLINE
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