Oncogenes with potential nuclear function: myc, myb and fos. 1986

R N Eisenman, and C B Thompson

The protein products of the retroviral oncogenes, v-myc, v-myb and v-fos, and their normal cellular counterparts, the c-myc, 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. The cellular forms of all three genes are normally expressed in a variety of cell types during proliferation and have RNA and protein products with short half-lives, which is consistent with the idea that they may have regulatory roles. Studies have shown that both c-myc and c-fos are induced during the stimulation of quiescent cells to enter the cell cycle and are continually expressed in replicating cells. In contrast, c-myb levels are greatest in cells as they prepare to enter and traverse S phase. Both c-myc and c-myb expression cease as cells terminally differentiate, whereas in some cell types c-fos is induced during differentiation. 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 some cell types. In most cell types, c-myc and c-myb expression is controlled primarily by posttranscriptional mechanisms, whereas c-fos expression 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. Taken together, these data suggest that all three nuclear oncogenes have distinct regulatory functions with respect to cellular proliferation and differentiation. Several models for function are discussed.

UI MeSH Term Description Entries
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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