The transcription factor C/EBPα is more potent than C/EBPβ in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a “domain swapping” approach to assess biological effects, modulation of gene expression, and binding to C/EBPα-regulated promoters by wild-type and chimeric C/EBPα/C/EBPβ proteins. Wild-type and N-C/EBPα+ C/EBPβ-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBPβ and N-C/EBPβ+C/EBPα-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBPα and N-C/EBPα+C/EBPβ-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBPα or C/EBPβ inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBPα. Gene expression profiles induced by C/EBPα resembled those modulated by N-C/EBPα+C/EBPβ-DBD, whereas C/EBPβ induced a pattern similar to that of N-C/EBPβ+C/EBPα-DBD. C/EBPα activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBPα-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells.

The biological effects of C/EBPalpha in K562 cells depend on the potency of the N-terminal regulatory region, not on specificity of the DNA binding domain / Ferrari, Giovanna; Mariani, Sa; Novi, Chiara; Cattelani, Sara; Pecorari, Luisa; Corradini, Francesca; Soliera, Angela Rachele; Manzotti, Gloria; Fragliasso, Valentina; Zhang, Y; Martinez, Rv; Lam, Ew; Guerzoni, C; Calabretta, Bruno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 285:(2010), pp. 30837-30850. [10.1074/jbc.M110.128272]

The biological effects of C/EBPalpha in K562 cells depend on the potency of the N-terminal regulatory region, not on specificity of the DNA binding domain.

FERRARI, Giovanna;NOVI, CHIARA;CATTELANI, Sara;PECORARI, Luisa;CORRADINI, Francesca;SOLIERA, Angela Rachele;MANZOTTI, GLORIA;FRAGLIASSO, VALENTINA;CALABRETTA, Bruno
2010

Abstract

The transcription factor C/EBPα is more potent than C/EBPβ in inducing granulocitic differentiation and inhibiting BCR/ABL-expressing cells. We took a “domain swapping” approach to assess biological effects, modulation of gene expression, and binding to C/EBPα-regulated promoters by wild-type and chimeric C/EBPα/C/EBPβ proteins. Wild-type and N-C/EBPα+ C/EBPβ-DBD induced transcription of the granulocyte-colony stimulating factor receptor (G-CSFR) gene, promoted differentiation, and suppressed proliferation of K562 cells vigorously; instead, wild-type C/EBPβ and N-C/EBPβ+C/EBPα-DBD had modest effects, although they bound the G-CSFR promoter like wild-type C/EBPα and N-C/EBPα+C/EBPβ-DBD. Chimeric proteins consisting of the TAD of VP16 and the DBD of C/EBPα or C/EBPβ inhibited proliferation and induced differentiation of K562 cells as effectively as wild-type C/EBPα. Gene expression profiles induced by C/EBPα resembled those modulated by N-C/EBPα+C/EBPβ-DBD, whereas C/EBPβ induced a pattern similar to that of N-C/EBPβ+C/EBPα-DBD. C/EBPα activation induced changes in the expression of more cell cycle- and apoptosis-related genes than the other proteins and enhanced Imatinib-induced apoptosis of K562 cells. Expression of FOXO3a, a novel C/EBPα-regulated gene, was required for apoptosis but not for differentiation induction or proliferation inhibition of K562 cells.
285
30837
30850
The biological effects of C/EBPalpha in K562 cells depend on the potency of the N-terminal regulatory region, not on specificity of the DNA binding domain / Ferrari, Giovanna; Mariani, Sa; Novi, Chiara; Cattelani, Sara; Pecorari, Luisa; Corradini, Francesca; Soliera, Angela Rachele; Manzotti, Gloria; Fragliasso, Valentina; Zhang, Y; Martinez, Rv; Lam, Ew; Guerzoni, C; Calabretta, Bruno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 285:(2010), pp. 30837-30850. [10.1074/jbc.M110.128272]
Ferrari, Giovanna; Mariani, Sa; Novi, Chiara; Cattelani, Sara; Pecorari, Luisa; Corradini, Francesca; Soliera, Angela Rachele; Manzotti, Gloria; Fragliasso, Valentina; Zhang, Y; Martinez, Rv; Lam, Ew; Guerzoni, C; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/645590
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