Myc target in myeloid cells-1, a novel c-Myc target, recapitulates multiple c-Myc phenotypes.
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.
Yin
Xiaoying
X
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, USA.
Grove
Linnette
L
Rogulski
Kenneth
K
Prochownik
Edward V
EV
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D002352:Carrier Proteins; D018076:DNA, Complementary; D008164:Luminescent Proteins; C458512:Myct1 protein, mouse; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins