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J Biol Chem. 2002 May 31;277(22):19998-20010. Epub 2002 Mar 21.

Myc target in myeloid cells-1, a novel c-Myc target, recapitulates multiple c-Myc phenotypes.

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  • 1Section 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, USA.

Abstract

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.

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