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 constr...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-02, Vol.272 (9), p.5594-5599
Main Authors: Mao, Shifeng, Neale, GeoffreyA. M., Goorha, Rakesh M.
Format: Article
Language:English
Subjects:
Animals
Binding Sites
COS Cells
DNA - metabolism
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Genes, Reporter
Metalloproteins - chemistry
Metalloproteins - metabolism
Polymerase Chain Reaction
Proline
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - metabolism
T-Lymphocytes - chemistry
Transcription Factors - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.9.5594