tom-1, a novel v-Myb target gene expressed in AMV- and E26-transformed myelomonocytic cells

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Abstract
The retroviral oncogene v‐myb is a mutated and truncated version of the c‐myb proto‐oncogene and encodes a transcription factor (v‐Myb) that specifically transforms myelomonocytic cells. Two different variants of v‐myb, transduced independently by the oncogenic chicken retroviruses AMV and E26, have been characterized. It is believed that both variants of v‐Myb transform myelomonocytic cells by affecting the expression of specific genes; however, no target genes common to both oncogenic viruses have been identified. Here, we describe the identification of a novel v‐Myb target gene, designated as tom‐1 (target of myb 1). The tom‐1 gene has two promoters, one of which is Myb‐inducible. tom‐1 is expressed at elevated levels in AMV‐transformed as well as in E26‐transformed myeloid cells. We show that tom‐1 activation by v‐Myb does not require de novo protein synthesis and that the Myb‐inducible tom‐1 promoter contains a functional Myb binding site. Thus, tom‐1 is the first example of a direct target gene for both oncogenic forms of the v‐myb gene. Further analysis of the Myb‐inducible tom‐1 promoter shows that a C/EBP binding site is juxtaposed to the Myb binding site and that C/EBP is required for the Myb‐dependent activation of the promoter. Together with previous work our results suggest that C/EBP may be a general cooperation partner for v‐Myb in myelomonocytic cells.