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7 Nuclear Oncogenes

Robert N. Eisenman


A. Final Steps in the Mitogenic Pathway
The early work on papovavirus tumor antigens taught us that the cell nucleus was likely to be the stage upon which proteins involved in cell transformation acted. It was something of a surprise when the first wave of studies on retroviral oncogenes and their cellular counterparts produced a picture of oncoprotein action as largely confined to the cytoplasm and the plasma membrane. Indeed, experiments using enucleated cells suggested that at least the multiple morphological alterations induced by one well-studied oncogene (v-src) could occur in the absence of a nucleus (Beug et al. 1978). Thus, for many workers involved in the initial characterization of retroviral oncoproteins, the subcellular fraction containing nuclei was usually discarded when cells were lysed for studies on oncogene function. This picture has changed dramatically in recent years, since it has become apparent that an important set of proto-oncogenes encode proteins that are predominantly localized in the nucleus. These include the myc family, fos, myb, erbA, jun, p53, the less-studied ski, and probably rel and ets. These genes, their human chromosome locations, and some of their general properties are listed in Table 1. In addition, the protein product of the retinoblastoma “anti-oncogene,” recently found to be mutated in several types of tumors, is also nuclear (see Chapter 11).

The nuclear localization of this group of cellular oncoproteins indicated a functionally distinct class of oncogenes and suggested as much diversity in oncoprotein function as in...

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