Redundant functions of B-Myb and c-Myb in differentiating myeloid cells

Josée Golay, Vania Broccoli, Gian Maria Borleri, Eugenio Erba, Mario Faretta, Luca Basilico, Guo Guang Ying, Gina Piccinini, Linda H. Shapiro, Josip Lovrić, Michael Nawrath, Karin Mölling, Alessandro Rambaldi, Martino Introna

Research output: Contribution to journalArticle

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Abstract

We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function. GFD8 cells are dependent for growth on granulocyte- macrophage colony-stimulating factor and differentiate in response to phorbol myristate acetate (PMA). We have stably transfected this cell line with constructs constitutively expressing c-Myb or B-Myb. Deregulated expression of both c-Myb and B-Myb inhibited the differentiation observed in response to PMA and, in particular, the induction of the CD11b and CD11c antigens on the cell surface, and the induction of adherence. Furthermore, c-Myb and B-Myb enhanced expression of CD13 upon PMA treatment. Although deregulated Myb expression did not alter the growth factor dependence of the cells, it led to an increase in G2 relative to G1 arrest in cells induced to differentiate in response to PMA, whereas control vector-transfected cells were blocked mostly in G1. This decrease in G1 block took place despite normal induction of the cyclin-dependent kinase inhibitor protein p21 (CIP1/WAF1). Thus, GFD8 cells stably expressing the human B-Myb protein behaved in a manner indistinguishable from those stably expressing c-Myb for both differentiation and cell cycle parameters. In agreement with these findings and differently from most previous reports, transactivation assays show that B-myb can indeed act as a strong activator of transcription. Finally, we demonstrated that although the DNA-binding domain of c-myb is required for both the differentiation block and the shift in cell cycle after PMA treatment, phosphorylation by casein kinase II and mitogen-activated protein kinase at positions 11 and 12 or 532 of c-myb, respectively, are not. We conclude that c-Myb and B-Myb may activate a common cellular program in the GFD8 cell line involved in both differentiation and cell cycle control.

Original languageEnglish
Pages (from-to)1305-1316
Number of pages12
JournalCell Growth and Differentiation
Volume8
Issue number12
Publication statusPublished - Dec 1997

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Myeloid Cells
Tetradecanoylphorbol Acetate
Cell Line
CD11c Antigens
CD11b Antigens
Cell Cycle
Cyclin-Dependent Kinase Inhibitor Proteins
myb Genes
Cyclin-Dependent Kinase Inhibitor p21
Casein Kinase II
Myeloid Leukemia
Proto-Oncogenes
Granulocyte-Macrophage Colony-Stimulating Factor
Cell Cycle Checkpoints
Mitogen-Activated Protein Kinases
Transcriptional Activation
Intercellular Signaling Peptides and Proteins
Phosphorylation
DNA
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Golay, J., Broccoli, V., Borleri, G. M., Erba, E., Faretta, M., Basilico, L., ... Introna, M. (1997). Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. Cell Growth and Differentiation, 8(12), 1305-1316.

Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. / Golay, Josée; Broccoli, Vania; Borleri, Gian Maria; Erba, Eugenio; Faretta, Mario; Basilico, Luca; Ying, Guo Guang; Piccinini, Gina; Shapiro, Linda H.; Lovrić, Josip; Nawrath, Michael; Mölling, Karin; Rambaldi, Alessandro; Introna, Martino.

In: Cell Growth and Differentiation, Vol. 8, No. 12, 12.1997, p. 1305-1316.

Research output: Contribution to journalArticle

Golay, J, Broccoli, V, Borleri, GM, Erba, E, Faretta, M, Basilico, L, Ying, GG, Piccinini, G, Shapiro, LH, Lovrić, J, Nawrath, M, Mölling, K, Rambaldi, A & Introna, M 1997, 'Redundant functions of B-Myb and c-Myb in differentiating myeloid cells', Cell Growth and Differentiation, vol. 8, no. 12, pp. 1305-1316.
Golay J, Broccoli V, Borleri GM, Erba E, Faretta M, Basilico L et al. Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. Cell Growth and Differentiation. 1997 Dec;8(12):1305-1316.
Golay, Josée ; Broccoli, Vania ; Borleri, Gian Maria ; Erba, Eugenio ; Faretta, Mario ; Basilico, Luca ; Ying, Guo Guang ; Piccinini, Gina ; Shapiro, Linda H. ; Lovrić, Josip ; Nawrath, Michael ; Mölling, Karin ; Rambaldi, Alessandro ; Introna, Martino. / Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. In: Cell Growth and Differentiation. 1997 ; Vol. 8, No. 12. pp. 1305-1316.
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abstract = "We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function. GFD8 cells are dependent for growth on granulocyte- macrophage colony-stimulating factor and differentiate in response to phorbol myristate acetate (PMA). We have stably transfected this cell line with constructs constitutively expressing c-Myb or B-Myb. Deregulated expression of both c-Myb and B-Myb inhibited the differentiation observed in response to PMA and, in particular, the induction of the CD11b and CD11c antigens on the cell surface, and the induction of adherence. Furthermore, c-Myb and B-Myb enhanced expression of CD13 upon PMA treatment. Although deregulated Myb expression did not alter the growth factor dependence of the cells, it led to an increase in G2 relative to G1 arrest in cells induced to differentiate in response to PMA, whereas control vector-transfected cells were blocked mostly in G1. This decrease in G1 block took place despite normal induction of the cyclin-dependent kinase inhibitor protein p21 (CIP1/WAF1). Thus, GFD8 cells stably expressing the human B-Myb protein behaved in a manner indistinguishable from those stably expressing c-Myb for both differentiation and cell cycle parameters. In agreement with these findings and differently from most previous reports, transactivation assays show that B-myb can indeed act as a strong activator of transcription. Finally, we demonstrated that although the DNA-binding domain of c-myb is required for both the differentiation block and the shift in cell cycle after PMA treatment, phosphorylation by casein kinase II and mitogen-activated protein kinase at positions 11 and 12 or 532 of c-myb, respectively, are not. We conclude that c-Myb and B-Myb may activate a common cellular program in the GFD8 cell line involved in both differentiation and cell cycle control.",
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AU - Golay, Josée

AU - Broccoli, Vania

AU - Borleri, Gian Maria

AU - Erba, Eugenio

AU - Faretta, Mario

AU - Basilico, Luca

AU - Ying, Guo Guang

AU - Piccinini, Gina

AU - Shapiro, Linda H.

AU - Lovrić, Josip

AU - Nawrath, Michael

AU - Mölling, Karin

AU - Rambaldi, Alessandro

AU - Introna, Martino

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