Cis Regulatory Control of mos Oncogene Expression
The viral and cellular homologs of the mos oncogene have been useful for studying the molecular elements required for cell transformation. These studies provided the first direct comparison of a viral oncogene and its cellular counterpart (8,14) and demonstrated that the cellular mos could be activated by viral sequences that cause cell transformation (14). Subsequently, it was shown that the proviral.transcription control element or long terminal repeat (LTR) and its enhancer was responsible for activation of the mouse c-mos (1,2,10,21). The more difficult task of identifying the mechanism by which the mos oncogene causes expression of the transformed phenotype remains to be solved. One approach to this problem has been to study proto-oncogene expression which can reveal important information about possible function. However, because the mos proto-oncogene is expressed at very low levels (15), it escaped detection for many years (5,6,13), and we, therefore, studied the biological activity of LTRactivated c-mos as a means of identifying important regulatory elements within the normal proto-oncogene locus. We first discovered an element called the upstream mouse sequence (UMS) located approximately 1.5 kilo-bases (kb) upstream from c-mosmu. This sequence prevented c-mos activation by a downstream LTR (14,22). UMS was subsequently shown to have both polyadenylation and transcription termination functions (12,22). We identified several regions in mos proto-oncogene loci from three different species, mouse (c-mosmff), human (c-moshu) and chicken (c-mosch) (12,22;Schmidt, in preparation) which reduce biological transforming activity. The c-mosmu sequence has been most extensively characterized.
KeywordsLong Terminal Repeat Thymidine Kinase Transforming Activity Cellular Oncogene Murine Sarcoma Virus
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