Deletion of the beta-turn/alpha-helix motif at the exon 2/3 boundary of human c-Myc leads to the loss of its immortalizing function.
The protein product (c-Myc) of the human c-myc proto-oncogene carries a beta-turn/alpha-helix motif at the exon2/exon3 boundary. The amino acid (aa) sequence and secondary structure of this motif are highly conserved among several nuclearly localized oncogene products, c-Myc, N-Myc, c-Fos, SV40 large T and adenovirus (Ad) Ela. Removal of this region from Ad E1a results in the loss of the transforming properties of the virus without destroying its known transregulatory functions. In order to analyse whether deletion of the above-mentioned region from c-Myc has a similar effect on its transformation activity, we constructed a deletion mutant (c-myc delta) lacking the respective aa at the exon2/exon3 boundary. In contrast to the c-myc wild-type gene product, constitutive expression of c-myc delta does not lead to the immortalization of primary mouse embryo fibroblast cells (MEF cells). This result indicates that c-Myc and Ad El a share a common domain which is involved in the transformation process by both oncogenes.