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

作　　者：Xueting Zhang Chenke Ma Yuchen Lu Jing Wang Hongfang Yun Hui Jiang Mengyao Wu Xiaoyao Feng Wenbin Gai Guanglei Xu Hongbin Deng Jiannan Feng Wanli Liu Taoxing Shi Qianqian Cheng Jiyan Zhang 

机构地区：[1]Beijing Institute of Basic Medical Sciences,Beijing,China [2]University of South China,Hengyang Medical School,Hengyang,China [3]Anhui Medical University,Hefei,China [4]Henan University Joint National Laboratoryfor AntibodyDrug Engineering,Kaifeng,China [5]institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,China [6]National Engineering Research Center for Emergence Drugs,Beijing Institute of Pharmacology and Toxicology,Bejing,China [7]Institute of Life Sciences,Tsinghua University,Beijing,China [8]Chinese Institute for Brain Research,Bejing,China

出　　处：《Cellular & Molecular Immunology》2024年第11期1282-1295,共14页中国免疫学杂志(英文版)

基　　金：supported by grants from the National Natural Science Foundation of China(81930027,92169207,and 82172298).

摘　　要：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.

关 键 词：RACK1 PAX5 UBIQUITINATION B-cell development BCR signaling 

分 类 号：Q78[生物学—分子生物学]