Determination of the c-MYC DNA-binding site.
The carboxyl terminus of the protein encoded by the c-MYC protooncogene has similarity to the helix-loop-helix family of DNA-binding proteins and recognizes a six-nucleotide-long DNA sequence. We have used in vitro-translated c-MYC protein to further define its DNA-binding specificity. The hexanucleotide originally identified is necessary for DNA binding by c-MYC, but not sufficient; the c-MYC target site is a 12-nucleotide-long palindrome. This site is present within regulatory regions of genes that are expressed during cell growth. Point mutations within the helix-loop-helix motif of c-MYC abolish DNA-binding and transforming activities, indicating that c-MYC acts as a DNA-binding protein to transform cells. c-MYC may transform cells by activating transcription of genes required for cell division.
Halazonetis
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Department of Cancer Research, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Kandil
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D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016259:Genes, myc; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D010957:Plasmids; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D016271:Proto-Oncogene Proteins c-myc