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J. Biol. Chem., Vol. 277, Issue 22, 19998-20010, May 31, 2002

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Myc Target in Myeloid Cells-1, a Novel c-Myc Target, Recapitulates Multiple c-Myc Phenotypes^*

Xiaoying Yin, Linnette Grove, Kenneth Rogulski, and Edward V. Prochownik^§¶

From the  Section of Hematology/Oncology, Children's Hospital of Pittsburgh, the ^§ Department of Molecular Genetics and Biochemistry, the University of Pittsburgh, and the ^¶ University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213

Using cDNA microarrays, we recently identified a large number of transcripts that are regulated differentially by the c-Myc oncoprotein in myeloid cells. Here, we characterize one of these, termed MT-MC1 (Myc Target in Myeloid Cells-1). MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc·Max heterodimers. Mutation of either site abrogates DNA binding by c-Myc·Max and renders the promoter c-Myc unresponsive. Finally, MT-MC1 regulates the expression of several other c-Myc target genes. MT-MC1 represents a proximal and direct c-Myc target that recapitulates many of the properties typically associated with Myc oncoprotein overexpression.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY09114.

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