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c-Jun N-terminal kinase (JNK) is required for survival and proliferation of B-lymphoma cells
| Content Provider | Scilit |
|---|---|
| Author | Gururajan, Murali Chui, Roger Karuppannan, Anbu Kumar Ke, Jiyuan Jennings, C. Darrell Bondada, Subbarao |
| Copyright Year | 2005 |
| Description | 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 G2/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 Egr-1 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. (Blood. 2005;106:1382-1391) |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895189/pdf |
| Ending Page | 1391 |
| Page Count | 10 |
| Starting Page | 1382 |
| DOI | 10.1182/blood-2004-10-3819 |
| Journal | Blood |
| Issue Number | 4 |
| Volume Number | 106 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2005-08-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Apoptosis Small Interfering Rna Protein Survival Proliferation Lymphoma Jnk Jun Egr Cd40 Journal: Blood (Vol- 78, Issue- 4) |
| Content Type | Text |
| Resource Type | Article |