c-Jun N-terminal kinase (JNK) is required for survival and proliferation of B-lymphoma cells

Murali Gururajan, Roger Chui, Anbu K. Karuppannan, Jiyuan Ke, C. Darrell Jennings, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Several primary murine and human B lymphomas and cell lines were found to constitutively express high levels of the activated form of c-jun N-terminal kinase (JNK), a member of the mitogen-activated protein (MAP) kinase family. Proliferation of murine B lymphomas CH31, CH12.Lx, BKS-2, and WEHI-231 and the human B lymphomas BJAB, RAMOS, RAJI, OCI-Ly7, and OCI-Ly10 was strongly inhibited by SP600125, an anthrapyrazolone inhibitor of JNK, in a dose-dependent manner. The lymphoma cells underwent apoptosis and arrested at the G 2/M phase of cell cycle. Furthermore, JNK-specific small interfering RNA (siRNA) inhibited the growth of both murine and human B lymphomas. Thus in the B-lymphoma model, JNK appears to have a unique prosurvival role. Survival signals provided by CD40 and interleukin-10 (IL-10) together reversed the growth inhibition induced by the JNK inhibitor. c-Myc protein levels were reduced in the presence of both SP600125 and JNK-specific siRNA, and CD40 ligation restored c-Myc levels. Moreover, Bcl-xL rescued WEHI-231 cells from apoptosis induced by the JNK inhibitor. The JNK inhibitor also reduced levels of early growth response gene-1 (Egr-1) protein, and overexpressing EgM partially rescued lymphoma cells from apoptosis. Thus, JNK may act via c-Myc and Egr-1, which were shown to be important for B-lymphoma survival and growth.

Original languageEnglish
Pages (from-to)1382-1391
Number of pages10
JournalBlood
Volume106
Issue number4
DOIs
StatePublished - Aug 15 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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