Hann, S. R., King, M. W., Bentley, D. L., Anderson, C. W. & Eisenman, R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell 52, 185-195

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Cell (Impact Factor: 32.24). 02/1988; 52(2):185-95. DOI: 10.1016/0092-8674(88)90507-7
Source: PubMed


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.

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    • "RAN translation occurs independent of the canonical AUG codon and has been demonstrated in vitro and in vivo (Hann et al., 1988; Kozak, 1989; Peabody, 1989). Recent studies have confirmed that despite the absence of an upstream AUG codon, RAN translation of repeat expansion tracks can occur in all 3 0 reading frames from both the sense and antisense transcripts (SCA8 example, Fig. 3). "
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    • "Our initial investigation into the origin of these three Caytaxin isoforms revealed that Caytaxin is one of few proteins consisting of multiple isoforms that are generated by different methionine translational start sites (Fig. 3C & D). This phenomenon is more often found in yeast proteins as well as in transcription factors and oncogenes [26] such as the cell-regulation gene c-Myc, which encodes three c-Myc protein isoforms originating from non-AUG and AUG codons [27], [28]. We identified two independent AUG start codons directly responsible for the production of the two larger Caytaxin isoforms. "
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    PLoS ONE 11/2012; 7(11):e50570. DOI:10.1371/journal.pone.0050570 · 3.23 Impact Factor
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    • "The extensive upstream non-AUG initiation we observe is likely to regulate protein synthesis from specific transcripts in response to global changes in initiation. It is also regulated during EB formation, suggesting a global link with growth and proliferation, and is involved in the synthesis of functional proteins, including the well-studied oncogene and pluripotency factor Myc (Hann et al., 1988). More broadly, it has been implicated in the production of peptides for immune surveillance (Malarkannan et al., 1999), and additional roles will likely emerge as we understand more about which non-AUG codons are used and how this selection is regulated. "
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