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Originally published In Press as doi:10.1074/jbc.M300080200 on January 13, 2003
J. Biol. Chem., Vol. 278, Issue 13, 11480-11488, March 28, 2003
c-Myc Is Essential but Not Sufficient for c-Myb-mediated Block of
Granulocytic Differentiation*
Atul
Kumar §¶ ,
Clement M.
Lee , and
E. Premkumar
Reddy **
From the Fels Institute for Cancer Research and
Molecular Biology and the § M.D./Ph.D. Program, Temple
University School of Medicine, Philadelphia, Pennsylvania 19140 and the
¶ Department of Medicine, Montefiore Medical Center, Bronx, New
York 10467
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.
*
This work was supported by Grant CA79086 from the NCI,
National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Both authors contributed equally to this work.
**
To whom correspondence should be addressed: Fels Institute for
Cancer Research and Molecular Biology, Temple University School of
Medicine, 3307 N. Broad St., Philadelphia, PA 19140. Tel.: 215-707-4307; Fax: 215-707-1454; E-mail: reddy@unix.temple.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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