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J. Biol. Chem., Vol. 277, Issue 38, 34815-34825, September 20, 2002
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From the Department of Biochemistry and Molecular Biology, School
of Biological Sciences, University of Southampton, Bassett Crescent
East, Southampton SO16 7PX, United Kingdom
N-Myc is a member of the Myc family of
transcription factors that have been shown to play a pivotal
role in cell proliferation and differentiation. In this report, we have
investigated the relationship between N-Myc and the developmental
control gene Pax-3. Using transient transfection assays, we
show that the Pax-3 promoter is activated by both N-Myc-Max
and c-Myc-Max. Moreover, we show that Myc regulation of
Pax-3 promoter activity is dependent upon a noncanonical E
box site in the 5' promoter region of Pax-3. In addition,
we show that ectopic expression of both N-Myc and c-Myc leads to
increased expression of Pax-3 mRNA. Furthermore, we
show that Pax-3 mRNA expression is cell cycle-regulated
and that the 5' promoter region of Pax-3 (bp
The Expression of the Developmentally Regulated Proto-oncogene
Pax-3 Is Modulated by N-Myc*
1578 to +56)
can direct cell cycle-dependent gene expression with
kinetics similar to that of the endogenous transcript. Site-directed
mutagenesis of the E box site within the Pax-3 promoter
significantly altered the pattern of expression through the cell cycle.
These results suggest that the Myc family of transcription factors may
modulate Pax-3 expression in vivo.
*
This work was supported by the Wessex Medical Trust.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.
To whom correspondence should be addressed. Tel.: 23-80592948;
Fax: 23-80594459; E-mail: KAL@soton.ac.uk.
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