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Papers In Press, published online ahead of print January 13, 2003
Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania 19140
Corresponding Author: reddy{at}unix.temple.edu
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 over-expression of c-Myb in 32Dcl3 cells results in the over-expression 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 lead 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.
J. Biol. Chem, 10.1074/jbc.M300080200
Submitted on January 5, 2003
Revised on January 13, 2003
Accepted on January 13, 2003
C-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic differentiation
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