Human N-myc is closely related in organization and nucleotide sequence to c-myc

Abstract

N-myc, a cellular gene related to the c-myc proto-oncogene, was originally identified on the basis of its very frequent amplification and overexpression in a restricted set of tumours, most notably human neuroblastomas. That N-myc may have a causal role in the genesis of these tumours is suggested by the observation that in the rat embryo fibroblast co-transformation assay it has a transforming potential similar to that of c-myc. The apparent structural and functional homology of N-myc and c-myc suggests that they may be members of the same protooncogene family. However, despite these apparent similarities, expression of the two genes appears to be dramatically different with respect to tumour specificity, as well as tissue and developmental stage specificity. To further elucidate the common and unique aspects of N-myc and c-myc gene structure and function in normal and transformed cells, we have determined the organization of human N-myc and the nucleotide sequence of its messenger product, and we report here that N-myc and c-myc have a similar intron/exon structure and that their protein products share regions of significant homology.

Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

“…The probes for detecting the ALK genome were prepared using the RT -PCR product (843 bp fragment) encoded the juxtamembrane segment of the ALK cDNA (3938 -4781) . The probe for the N-myc gene was prepared from the 2 kb BglII-EcoRI fragment of the genomic clone, pN-myc2238, kindly provided by Dr Y Taya, which was to detect 3.8 kb of the genomic N-myc DNA digested by EcoRI (Kohl et al, 1986;Stanton et al, 1986). As a control we used the probe for detecting ShcC gene, that was obtained by digesting pCMV1-T7N-Shc, human ShcC cDNA, kindly provided by Nakamura et al (1996b).…”

L-myc cooperates with ras to transform primary rat embryo fibroblasts.

“…Members of this family include the well-characterized c-myc and N-myc genes and the more recently described L-myc gene (1,2,8,12). All three members have similar overall structures, consisting of three exons with extensive areas of homology in the protein-coding regions of exons 2 and 3.…”

Two N-myc polypeptides with distinct amino termini encoded by the second and third exons of the gene.

“…Overall homology of the deduced amino acid sequences is 32%, and distinct regions throughout the proteins are nearly identical (6,43,50). Interestingly, even the nonhomologous coding regions are highly conserved between the human and mouse N-myc genes, which show an overall homology of over 85% (13,23,50,51). This suggests that the two genes perform similar but not identical functions.…”

“…Three ATG codons were identified at the 5' end of the single long open reading frame of N-myc. The first of these ATGs was suggested to function as a translational initiation codon, since this codon and the downstream coding sequence were conserved in human and murine N-myc (23). Alternatively, the second ATG was regarded as the most likely initiation codon (50) because it was in the best sequence context conforming to established sites of translational initiation (27).…”

“…The probable coding sequence of the N-myc gene was first deduced from the genomic sequences of both the human (23,50) and mouse (13,51) N-myc genes. Three ATG codons were identified at the 5' end of the single long open reading frame of N-myc.…”