Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase

Gem S. Burgess, Elizabeth A. Williamson, Larry D. Cripe, Sara Litz-Jackson, Jay A. Bhatt, Kurt Stanley, Mark J. Stewart, Andrew Kraft, Harikrishna Nakshatri, H. Scott Boswell

Research output: Contribution to journalArticle

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Abstract

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-los 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-los 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.

Original languageEnglish (US)
Pages (from-to)2450-2460
Number of pages11
JournalBlood
Volume92
Issue number7
StatePublished - Oct 1 1998
Externally publishedYes

Fingerprint

jun Genes
JNK Mitogen-Activated Protein Kinases
Transcription Factor AP-1
Interleukin-3
Proto-Oncogene Proteins c-jun
Transcription
Proteins
Myeloid Cells
Phosphotransferases
Cells
Cell Line
Philadelphia Chromosome
Chromosomes
Chemical analysis
Catalysis
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

Burgess, G. S., Williamson, E. A., Cripe, L. D., Litz-Jackson, S., Bhatt, J. A., Stanley, K., ... Boswell, H. S. (1998). Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase. Blood, 92(7), 2450-2460.

Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase. / Burgess, Gem S.; Williamson, Elizabeth A.; Cripe, Larry D.; Litz-Jackson, Sara; Bhatt, Jay A.; Stanley, Kurt; Stewart, Mark J.; Kraft, Andrew; Nakshatri, Harikrishna; Boswell, H. Scott.

In: Blood, Vol. 92, No. 7, 01.10.1998, p. 2450-2460.

Research output: Contribution to journalArticle

Burgess, GS, Williamson, EA, Cripe, LD, Litz-Jackson, S, Bhatt, JA, Stanley, K, Stewart, MJ, Kraft, A, Nakshatri, H & Boswell, HS 1998, 'Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase', Blood, vol. 92, no. 7, pp. 2450-2460.
Burgess GS, Williamson EA, Cripe LD, Litz-Jackson S, Bhatt JA, Stanley K et al. Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase. Blood. 1998 Oct 1;92(7):2450-2460.
Burgess, Gem S. ; Williamson, Elizabeth A. ; Cripe, Larry D. ; Litz-Jackson, Sara ; Bhatt, Jay A. ; Stanley, Kurt ; Stewart, Mark J. ; Kraft, Andrew ; Nakshatri, Harikrishna ; Boswell, H. Scott. / Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase. In: Blood. 1998 ; Vol. 92, No. 7. pp. 2450-2460.
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abstract = "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-los 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-los 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.",
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AU - Burgess, Gem S.

AU - Williamson, Elizabeth A.

AU - Cripe, Larry D.

AU - Litz-Jackson, Sara

AU - Bhatt, Jay A.

AU - Stanley, Kurt

AU - Stewart, Mark J.

AU - Kraft, Andrew

AU - Nakshatri, Harikrishna

AU - Boswell, H. Scott

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