Oncogenes with Potential Nuclear Function: myc, myb and fos

摘要

The protein products of the retroviral oncogenes, v-myc, v-myb and v-fos, and their normal cellular counterparts, the c-myb and c-fos proto-oncogenes, have been found to be localized predominantly in the nucleus. In view of the oncogenicity of the retroviral forms of these genes, it is probable that they have central roles in the nuclear events involved in cellular proliferation and differentiation. To investigate these possibilities, detailed studies on the expression of these 'nuclear oncogenes' have been performed. Unregulated expression of all three genes has distinct effects on cellular differentiation: myc seems to inhibit differentiation of several cell types when expressed at high levels; myb does not appear to effect differentiation in the systems in which it has been examined; and fos appears to be able to induce differentiation of so9me cell types. In most cell types, C-myc and c-myb expression is controlled primarily by post-transcriptional mechanisms, whereas c-fos expressions is regulated primarily at the transcriptional level. The protein products of these oncogenes are all phosphorylated and probably undergo additional modifications. The nuclear association of these proteins is complex and apparently takes multiple forms. The data suggest that all three nuclear oncogenes have distinct regulatory functions with respect to cellular proliferation and differentiation. Several models for the functions are discussed. Keywords: Nuclear oncogenes, Growth factors, Reprints; Mitogenesis, Cell cycle, Cell differentiation; Genes. (kt)