PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance of B-lymphoproliferative disorders

Abstract

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 kinase2 (RIP2) and subsequent activation of NF-κB signaling and anti-apoptosis genes expression in B-lymphoproliferative cells. Furthermore, PAX5 is able to interact with RIP1-3, modulating both RIP1- mediated TNFR and RIP2-mediated NOD1 and NOD2 pathways. Our findings describe a novel function of PAX5 in regulating RIP1 and RIP2 activation, which is at least involved in chemo drug-resistance in B-LPDs.