PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance in B-lymphoproliferative disorders.
Dong WangJingyu ChenRui LiGuolin WuZimin SunZhitao WangZhimin ZhaiFang FangYugang GuoYongjun ZhongMing JiangHuan XuMinhua ChenGuodong ShenJie SunBailing YanChundong YuZhigang TianWeihua XiaoPublished in: Journal of cell science (2016)
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.
Keyphrases
- protein kinase
- gene expression
- signaling pathway
- epstein barr virus
- binding protein
- cell cycle arrest
- oxidative stress
- induced apoptosis
- pi k akt
- cell death
- endoplasmic reticulum stress
- lps induced
- cell proliferation
- diffuse large b cell lymphoma
- mass spectrometry
- high resolution
- single cell
- inflammatory response
- toll like receptor
- simultaneous determination