c-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic differentiation.
The c-myb proto-oncogene plays a central role in hematopoiesis and encodes a major translational product of 75 kDa. c-Myb is highly expressed in immature hematopoietic cells, and its expression is down-regulated during terminal differentiation. Deregulated expression of c-Myb has been shown to block terminal differentiation of hematopoietic cells. Here we have studied the mechanism of action and the nature of target genes through which c-Myb mediates the block in differentiation of 32Dcl3 murine myeloid cells. We show that the ectopic overexpression of c-Myb in 32Dcl3 cells results in the overexpression of c-Myc. However, enforced expression of c-Myc in 32Dcl3 cells did not alter the normal pattern of differentiation. In addition, expression of dominant-negative mutants of c-Myc relieved c-Myb-mediated block in differentiation. These results led us to conclude that c-myc is a target gene of c-Myb and activation of the c-myc gene is a necessary event in Myb-mediated transformation. However, c-Myc expression alone is inadequate to elicit the phenotypic effects seen with Myb-mediated block in differentiation of myeloid cells, suggesting that activation of additional transcriptional targets by c-Myb plays a critical role in this process.
Kumar
Atul
A
Fels Institute for Cancer Research and Molecular Biology and the M.D./Ph.D. Program, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Lee
Clement M
CM
Reddy
E Premkumar
EP
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006098:Granulocytes / Q000166:cytology*; D051379:Mice; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D019076:Transgenes
D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D016179:Granulocyte Colony-Stimulating Factor