Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase
| Autor: | G S, Burgess, E A, Williamson, L D, Cripe, S, Litz-Jackson, J A, Bhatt, K, Stanley, M J, Stewart, A S, Kraft, H, Nakshatri, H S, Boswell |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Mitogen-Activated Protein Kinase Kinases
Transcription Genetic MAP Kinase Kinase 4 Macromolecular Substances Proto-Oncogene Proteins c-jun Recombinant Fusion Proteins Fusion Proteins bcr-abl JNK Mitogen-Activated Protein Kinases HL-60 Cells Hematopoietic Stem Cells Transfection Neoplasm Proteins Enzyme Activation Mice Cell Transformation Neoplastic Genes jun Leukemia Myelogenous Chronic BCR-ABL Positive Mutagenesis Site-Directed Tumor Cells Cultured Animals Humans Phosphorylation Protein Kinases Protein Processing Post-Translational |
| Zdroj: | Blood. 92(7) |
| ISSN: | 0006-4971 |
| Popis: | Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)-dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3-treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3-stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fos proteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome-positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|