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.