The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription
| Autor: | Gerard Grosveld, Arjan Buijs, Karel H. M. van Wely, Magda A. Meester-Smoor, Albert Jan Aarnoudse, Anita Hellemons, Ellen C. Zwarthoff, Pim den Besten, Anco C. Molijn |
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| Rok vydání: | 2003 |
| Předmět: |
Nucleocytoplasmic Transport Proteins
Cancer Research Oncogene Proteins Fusion Transcription Genetic Receptors Retinoic Acid Response element E-box Transcription coregulator Biology Sp3 transcription factor Genetics Animals Humans Molecular Biology General transcription factor Nuclear Proteins RNA-Binding Proteins rac GTP-Binding Proteins Cell biology DNA-Binding Proteins Retinoic acid receptor Transcription Coactivator COS Cells TAF2 Trans-Activators Cancer research Carrier Proteins HeLa Cells Transcription Factors |
| Zdroj: | Oncogene. 22:699-709 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1206124 |
| Popis: | The t(12;22) creates an MN1-TEL fusion gene leading to acute myeloid leukemia. The fusion partner TEL (ETV6) is a member of the ETS family of transcription factors. The nature of the other fusion partner, MN1, has not been investigated in detail until now. We recently described that MN1 activates the transcription activity of the moloney sarcoma virus long terminal repeat, indicating that this protein itself may act as a transcription factor. We show here that MN1 comprises multiple transcription activating domains. A search for a bound DNA sequence revealed that MN1 has affinity for retinoic acid responsive elements. A DR5 retinoic acid responsive element was observed in the LTR. The combination of MN1 and ligand-activated retinoic acid receptor leads to a synergistic induction of expression directed by the LTR. Cotransfection of MN1 with RAC3 or p300, known coactivators of retinoic acid receptors, leads to a further synergistic induction of transcription. In addition, the effect of MN1 can be inhibited by the wild-type adenovirus ElA protein that inhibits p300 function, but not by an E1A mutant lacking the p300-binding site. GAL4-MN1-mediated transcription can be enhanced directly by RAC3 and p300. Taken together, our results indicate that MN1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate RAR/RXR-mediated transcription through interaction with p160 and p300. |
| Databáze: | OpenAIRE |
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