The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.
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.
We report the isolation of a novel human POU domain encoding gene named RDC-1. The POU domain of the RDC-1 encoded protein is highly related to the POU domain potentially encoded by the rat brain-3 sequence and to that of the Drosophila I-POU protein; outside of the POU region, RDC-1 is unrelated to any previously characterized protein. The RDC-1 gene is expressed almost exclusively in normal tissues and transformed cells of neural origin. In the developing mouse and human fetus, RDC-1 is expressed in a spatially and temporally restricted pattern that suggests a critical role in the differentiation of neuronal tissues. In addition, RDC-1 is expressed in a unique subset of tumors of the peripheral nervous system including neuroepitheliomas and Ewing's sarcomas but not neuroblastomas. Based on its unique structural characteristics and expression pattern, we discuss potential functions for the RDC-1 protein.
The myc family of cellular oncogenes contains three well-defined members: c-myc, N-myc and L-myc. Additional structural and functional evidence now suggests that other myc-family oncogenes exist. The overall structure and organization of the c-, N-, and L-myc genes and transcripts are very similar. Each gene contains three exons: encoding a long 5' untranslated leader and a long 3' untranslated region. The proteins encoded by these myc genes share several stretches of significant homology. The conservation of sequences at the carboxyterminus of the L-myc protein suggests that it is also a DNA-binding, nuclear-associated protein. Each myc gene will cooperate with an activated Ha-ras oncogene to cause transformation of primary rat embryo fibroblasts. Characteristics of several new myc-family members are described.
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