Structure and expression of the murine L-myc gene.

Abstract

We have isolated a 12 kb clone from the murine genome which we show by DNA transfection studies to contain an entire functional L‐myc gene and the transcriptional promoter sequences necessary for its expression. We have also isolated a 3.1 kb cDNA sequence from a murine brain cDNA library which corresponds to most of the L‐myc mRNA. We have identified the L‐myc coding region within the genomic clone by a combination of S1 nuclease analyses. Northern blotting analyses and comparative nucleotide sequence analyses with the cDNA clone. The L‐myc gene appears to be organized similarly to the other well‐characterized myc‐family genes, c‐myc and N‐myc. The predicted amino acid coding sequence of the L‐myc gene indicates that the L‐myc protein is significantly smaller than c‐ and N‐myc, but is highly related. In particular, comparison of the N‐ and c‐myc protein sequences reveals seven relatively conserved regions interspersed among non‐conserved regions; the L‐myc gene retains five of these conserved regions but lacks two others. In addition, a portion of one highly conserved region is encoded within a different region of the L‐myc gene but, due to changes in the size of L‐myc exons relative to those of N‐ and c‐myc, maintains its overall position in the peptide backbone with respect to other conserved regions. We discuss these findings in the context of potential functional domains and the possibility of overlapping and distinct activities of myc‐family proteins.

Myc family oncoproteins function through a common pathway to transform normal cells in culture: cross-interference by Max and trans-acting dominant mutants.

“…L-zip encodes a mutant L-Myc protein with a deletion of amino acid residues 23-140. This construct was derived from the mouse L-myc cDNA (Legouy et al 1987). Both N-zip and L-zip are driven by the RSV/LTR and contain the SV40 polyadenylation signal described in c-zip.…”

“…early-passage REFs (Land et al 1983;Schwab et al 1985;Yancopoulos et al 1985;DePinho et al 1987a, b;Legouy et al 1987;Birrer et al 1988). In this assay, c-myc appears to be most oncogenically active, whereas N-myc and L-myc exhibit moderate and weak transforming activity, respectively (DePinho et al 1987a, b).…”

L-Myc protein synthesis is initiated by internal ribosome entry

“…The L-myc gene belongs to the myc family of proto-oncogenes and shares extensive sequence and functional homology with two other members of this intensely studied group, c-myc and N-myc (Nau et al 1985;Legouy et al 1987). Overexpression of all three genes has been associated with neoplasia and causes cell transformation (Boxer and Dang 2001;Lutz et al 2002;Pelengaris et al 2002;Strieder and Lutz 2002).…”

High frequency of myelomonocytic tumors in aging E mu L-myc transgenic mice.

“…Preparation of KNA and Northern blotting was as described (33). c-, hi-, and b,nyc probes and the probes specific for C# and VhJ558 have already been described (3,8,14,35,40). The Thy-1 probe is a 1.4-kb ApaI fragment isolated from the 3' untranslated region of the Thy-1 gene (41), thetis probe is a 1.3-kb fragment from the plasmid pros 1 (42).…”

“…All three genes have a similar three-exon structure and encode nuclear phosphoproteins that contain several regions of extensive homology in their amino acid sequences (1). The conservation of the individual myc genes through evolution suggests that they exert unique but related functions (2)(3)(4)(5)(6). Several studies have shown that myc gene products are involved in the regulation of cellular proliferation and differentiation, but their exact function remains to be elucidated (1).…”