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

doi:10.1242/jcs.183889

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

J Cell Sci. 2016 Jun 1;129(11):2261-72. doi: 10.1242/jcs.183889. Epub 2016 Apr 27.

Authors

Dong Wang¹, Jingyu Chen¹, Rui Li¹, Guolin Wu², Zimin Sun², Zhitao Wang³, Zhimin Zhai³, Fang Fang¹, Yugang Guo¹, Yongjun Zhong¹, Ming Jiang¹, Huan Xu¹, Minhua Chen¹, Guodong Shen¹, Jie Sun¹, Bailing Yan⁴, Chundong Yu⁵, Zhigang Tian¹, Weihua Xiao⁶

Affiliations

¹ Key Laboratory of Innate Immunity and Chronic Disease of CAS, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
² Department of Hematology, Anhui Provincial Hospital, 17 Lujiang Road, Hefei, Anhui Province 230001, China.
³ Department of Hematology, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui Province 230601, China.
⁴ Emergency Department, the First Hospital of Jilin University, Changchun 130021, China.
⁵ Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.
⁶ Key Laboratory of Innate Immunity and Chronic Disease of CAS, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China [email protected].

PMID: 27122187
DOI: 10.1242/jcs.183889

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 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.

Keywords: B-lymphoproliferative disorders; Drug resistance; NF-κB; PAX5; RIP2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
B-Lymphocytes / drug effects
B-Lymphocytes / metabolism*
Bortezomib / pharmacology
Bortezomib / therapeutic use
Carcinogenesis / metabolism
Carcinogenesis / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Resistance, Neoplasm* / drug effects
Humans
Lymphoproliferative Disorders / metabolism*
Lymphoproliferative Disorders / pathology
Models, Biological
NF-kappa B / metabolism*
Nod Signaling Adaptor Proteins / metabolism
PAX5 Transcription Factor / metabolism*
Protein Binding / drug effects
Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism*
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / pharmacology

Substances

Antineoplastic Agents
NF-kappa B
Nod Signaling Adaptor Proteins
PAX5 Transcription Factor
Tumor Necrosis Factor-alpha
Bortezomib
RIPK2 protein, human
Receptor-Interacting Protein Serine-Threonine Kinase 2