The human myc gene family: structure and activity of L-myc and an L-myc pseudogene.
We have determined the nucleotide sequence and transforming activity of the human L-myc gene and a processed L-myc pseudogene (L-myc psi). We demonstrate by cotransformation assays that a 10.6-kb EcoRI fragment derived from a human placental library contains a complete and functional L-myc gene including transcriptional regulatory sequences sufficient for expression in rat embryo fibroblasts. Organization of the L-myc gene was determined by comparing its sequence to those of the L-myc psi gene and an L-myc cDNA clone derived from a human small cell lung carcinoma. Our results show that L-myc has a three-exon organization similar to that of the c-myc and N-myc genes. The putative L-myc gene product consists of 364 amino acids and contains five of the seven homology regions highly conserved between c-myc and N-myc. These conserved regions are located along the entire length of the putative L-myc protein and are interspersed among nonconserved regions. While the putative L-myc gene product is of a smaller size when compared to the c- and N-myc proteins, the relative positions of certain conserved residues occur in corresponding locations along the peptide backbone of the three proteins. In addition, comparison of the human and murine L-myc gene sequences indicate that the relatively large 5' and 3' untranslated regions are evolutionarily conserved, but that these sequences are totally divergent between the L-, c-, and N-myc genes. Finally, we demonstrate that, like the N- and c-myc genes, the L-myc gene can cooperate with a mutant Ha-ras gene to cause malignant transformation of rat embryo fibroblasts in culture. Our analyses clearly prove that L-myc represents a functional member of the myc oncogene family and further delineate structural features that may be important for the common and divergent functions of the members of this gene family.
DePinho
R A
RA
Howard Hughes Medical Institute, New York.
Hatton
K S
KS
Tesfaye
A
A
Yancopoulos
G D
GD
Alt
F W
FW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D011544:Pseudogenes; D051381:Rats
D011518:Proto-Oncogene Proteins