T-cell proto-oncogene rhombotin-2 is a complex transcription regulator containing multiple activation and repression domains.
The LIM domain protein rhombotin-2 (RBTN-2/TTG-2/LMO2) is involved in many processes, including leukemogenesis and erythropoiesis. It is thought that the principle role of RBTN-2 in these processes is to regulate transcription. To examine the potential for RBTN-2 to modulate transcription, we constructed RBTN-2/GAL4 DNA-binding domain fusion proteins and measured their ability to activate transcription of a reporter gene construct. From these studies we identified a transcription activation domain within the NH2 terminus of RBTN-2. This activation domain was further localized within a proline-rich 19-amino acid region. A second activation domain of 11 amino acids was also identified. This domain was located within the COOH terminus of RBTN-2, and functioned in mammalian cells but not in yeast. Furthermore, the two LIM domains of RBTN-2 were shown to function as transcription repression domains. Each individual LIM domain acted as an independent transcription repression domain on a heterologous activation domain. However, in context of full-length RBTN-2, the LIM domains selectively repressed the NH2-terminal activation domain, but had no effect on the COOH-terminal domain. Overall, these results demonstrate that the T-cell oncogene RBTN-2 is a complex transcription factor possessing multiple transcription regulatory modules, including two activation domains and two repression domains.
Mao
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Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Neale
G A
GA
Goorha
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RM
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D017930:Genes, Reporter; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011392:Proline; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA; D011392:Proline