A degradation-resistant c-Myb mutant cooperates with Bcl-2 in enhancing proliferative potential and survival of hematopoietic cells.
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.
Corradini
Francesca
F
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA, USA. corraf@libero.it
Bussolari
Rita
R
Cerioli
Davide
D
Lidonnici
Maria Rosa
MR
Calabretta
Bruno
B
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
D007377:Interleukin-3; D050505:Mutant Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020598:Proto-Oncogene Proteins c-myb