A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas.
The c-myc gene comprises three exons with a single large AUG-initiated open reading frame extending from exon 2 through exon 3. Exon 1 lacks any AUG codons. Cells from a wide range of species produce two c-myc proteins that, while highly related, do not appear to arise from posttranslational interconversion. To understand the origin of the two proteins, we mapped them and analyzed the in vitro protein-coding capacity of c-myc cDNAs. Our findings show that the two proteins are derived from alternative translational initiations at the exon 2 AUG and at a non-AUG codon near the 3' end of exon 1, resulting in the production of proteins with distinct N termini. In Burkitt's lymphomas, the removal or specific mutation of exon 1 in c-myc translocations correlates with suppression of synthesis of the larger protein, and thus may contribute to the oncogenic activation of c-myc.
Hann
S R
SR
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
King
M W
MW
Bentley
D L
DL
Anderson
C W
CW
Eisenman
R N
RN
D000818:Animals; D005075:Biological Evolution; D002051:Burkitt Lymphoma / Q000235:genetics*; D002460:Cell Line; D002645:Chickens; D003062:Codon; D004274:DNA, Recombinant; D005091:Exons; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009154:Mutation; D010442:Peptide Chain Initiation, Translational; D010446:Peptide Fragments; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D014982:Xenopus laevis
D003062:Codon; D004274:DNA, Recombinant; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger