Structure, expression, and oncogenic activity of the myc gene family

The myc family of nuclear proto-oncogenes have emerged as genetic elements which are likely to playa significant role in the regulation of normal mammalian development and malignant transformation. The first cellular myc gene was discovered over a decade ago by Sheiness and Bishop who demonstrated the existence of a cellular homologue of an avian myelocytomatosis virus (v-myc) oncogene, designated c_myc. 1·2 Since that time, many laboratories have conducted an intensive search for additional myc-homologous sequences, culminating in the isolation of a group of highly-related genes comprising the myc family of nuclear proto-oncogenes.3-5 To date, the myc family consists of three well-characterized genes, c-, N-, and L-myc, as well as a number of myc-related pseudogenes, L-myc and Pmyc, and less well analyzed myc-related sequences.4.6-13 Initial studies have focused on myc gene structure, developmental and tumor expression, and in vitro oncogenic activity. These studies revealed that myc family oncogenes share a similar gene structure, 6-13 encode biochemically related gene products, 14-28 possess similar oncogenic activities,12.29-32 and are expressed in a distinctive temporal and spatial manner during normal mammalian development. 33-35 Although these properties suggest functional relatedness, the conservation of myc family members as distinct genes in phylogenetically distant species (e.g., fish,36 frogs,37 birds, 38 mice/. IO·11 and humans6,8.9,12.13) suggests important and unique biological functions which to this time remain obscure.