The c-myb gene is preferentially expressed in primitive hematopoietic cell and plays a central role in the control of cell proliferation, differentiation and survival by regulating the transcription of several genes implicated in these processes including the antiapoptotic Bcl-2. We show here that, compared to wild-type c-Myb, overexpression of a degradation resistant c-Myb mutant [Delta(358-452) c-Myb] enhances the clonogenic potential of hematopoietic progenitors as indicated by increased cytokine-dependent primary and secondary colony formation of Lin(-) Sca-1(+) Kit(+) mouse marrow cells. Moreover, proliferation assays of IL-3 dependent myeloid precursor 32Dcl3 cells co-expressing Bcl-2 and c-Myb indicate that these cells continue to proliferate in the absence of IL-3 and this effect is more apparent in cells expressing the degradation resistant Delta(358-452) c-Myb. Interestingly, overexpression of Delta(358-452) c-Myb is by itself sufficient to protect 32Dcl3 cells from apoptosis induced by IL-3 deprivation; moreover, these cells are also increased in number which most likely reflects the enhanced proliferative potential conferred by Delta(358-452) c-Myb to apoptosis-resistant cells
A degradation-resistant c-Myb mutant cooperates with Bcl-2 in enhancing proliferative potential and survival of hematopoietic cells / Corradini, Francesca; Bussolari, Rita; Cerioli, D; Lidonnici, Mr; Calabretta, Bruno. - In: BLOOD CELLS, MOLECULES, & DISEASES. - ISSN 1079-9796. - STAMPA. - 39:3(2007), pp. 292-296. [10.1016/j.bcmd.2007.06.002]
A degradation-resistant c-Myb mutant cooperates with Bcl-2 in enhancing proliferative potential and survival of hematopoietic cells
CORRADINI, Francesca;BUSSOLARI, Rita;CALABRETTA, Bruno
2007
Abstract
The c-myb gene is preferentially expressed in primitive hematopoietic cell and plays a central role in the control of cell proliferation, differentiation and survival by regulating the transcription of several genes implicated in these processes including the antiapoptotic Bcl-2. We show here that, compared to wild-type c-Myb, overexpression of a degradation resistant c-Myb mutant [Delta(358-452) c-Myb] enhances the clonogenic potential of hematopoietic progenitors as indicated by increased cytokine-dependent primary and secondary colony formation of Lin(-) Sca-1(+) Kit(+) mouse marrow cells. Moreover, proliferation assays of IL-3 dependent myeloid precursor 32Dcl3 cells co-expressing Bcl-2 and c-Myb indicate that these cells continue to proliferate in the absence of IL-3 and this effect is more apparent in cells expressing the degradation resistant Delta(358-452) c-Myb. Interestingly, overexpression of Delta(358-452) c-Myb is by itself sufficient to protect 32Dcl3 cells from apoptosis induced by IL-3 deprivation; moreover, these cells are also increased in number which most likely reflects the enhanced proliferative potential conferred by Delta(358-452) c-Myb to apoptosis-resistant cells
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