Translational regulation by oncogenic proteins may be a rapid and efficient mechanism to modulate gene expression. We report here the identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. Expression of CEBPB was repressed in 32D-BCR/ABL cells and reinduced by imatinib (STI571) via a mechanism that appears to depend on expression of the CUG-repeat RNA-binding protein CUGBP1 and the integrity of the CUG-rich intercistronic region of c/ebp beta mRNA. Constitutive expression or conditional activation of wildtype CEBPB induced differentiation and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA binding-deficient CEBPB mutant had no effect. The proliferation-inhibitory effect of CEBPB was, in part, mediated by the CEBPB-induced GADD45A gene. Because expression of CEBPB (and CEBPA) is low in the blast crisis (BC) stage of chronic myelogenous leukemia (CML) and is inversely correlated with BCR/ABL tyrosine kinase levels, these findings point to the therapeutic potential of restoring C/EBP activity in CML-BC and, perhaps, other types of acute leukemia.

Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BICRABL-expressing cells / Guerzoni, Clara; Bardini, M; Mariani, Sa; Ferrari, Giovanna; Neviani, P; Panne, Ml; Zhang, Y; Martinez, R; Perrotti, D; Calabretta, Bruno. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 107:10(2006), pp. 4080-4089. [10.1182/blood-2005-08-3181]

Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BICRABL-expressing cells

GUERZONI, Clara;FERRARI, Giovanna;CALABRETTA, Bruno
2006

Abstract

Translational regulation by oncogenic proteins may be a rapid and efficient mechanism to modulate gene expression. We report here the identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. Expression of CEBPB was repressed in 32D-BCR/ABL cells and reinduced by imatinib (STI571) via a mechanism that appears to depend on expression of the CUG-repeat RNA-binding protein CUGBP1 and the integrity of the CUG-rich intercistronic region of c/ebp beta mRNA. Constitutive expression or conditional activation of wildtype CEBPB induced differentiation and inhibited proliferation of 32D-BCR/ABL cells in vitro and in mice, but a DNA binding-deficient CEBPB mutant had no effect. The proliferation-inhibitory effect of CEBPB was, in part, mediated by the CEBPB-induced GADD45A gene. Because expression of CEBPB (and CEBPA) is low in the blast crisis (BC) stage of chronic myelogenous leukemia (CML) and is inversely correlated with BCR/ABL tyrosine kinase levels, these findings point to the therapeutic potential of restoring C/EBP activity in CML-BC and, perhaps, other types of acute leukemia.
2006
107
10
4080
4089
Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BICRABL-expressing cells / Guerzoni, Clara; Bardini, M; Mariani, Sa; Ferrari, Giovanna; Neviani, P; Panne, Ml; Zhang, Y; Martinez, R; Perrotti, D; Calabretta, Bruno. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 107:10(2006), pp. 4080-4089. [10.1182/blood-2005-08-3181]
Guerzoni, Clara; Bardini, M; Mariani, Sa; Ferrari, Giovanna; Neviani, P; Panne, Ml; Zhang, Y; Martinez, R; Perrotti, D; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/2728
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