PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance in B-lymphoproliferative disorders
Dong Wang, Jingyu Chen, Rui Li, Guolin Wu, Zimin Sun, Zhitao Wang, Zhimin Zhai, Fang Fang, Yugang Guo, Yongjun Zhong, Ming Jiang, Huan Xu, Minhua Chen, Guodong Shen, Jie Sun, Bailing Yan, Chundong Yu, Zhigang Tian, Weihua Xiao
Paired box protein 5 (PAX5) plays a lineage determination role in B-cell development. However, high expression of PAX5 has been also found in various malignant diseases, including B-lymphoproliferative disorders (B-LPDs), but its functions and mechanisms in these diseases are still unclear. Here, we show that PAX5 induces drug resistance through association and activation of receptor-interacting serine/threonine-protein kinase 2 (RIP2; also known as RIPK2), and subsequent activation of NF-κB signaling and anti-apoptosis gene expression in B-lymphoproliferative cells. Furthermore, PAX5 is able to interact with RIP1 and RIP3, modulating both RIP1-mediated TNFR and RIP2-mediated NOD1 and NOD2 pathways. Our findings describe a new function of PAX5 in regulating RIP1 and RIP2 activation, which is at least involved in chemotherapeutic drug resistance in B-LPDs.