Ligand-inducible interaction of the DRTP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells Journal Article
| Authors: | Shao, W. L.; Rosenauer, A.; Mann, K.; Chang, C. P. B.; Rachez, C.; Freedman, L. P.; Miller, W. H. |
| Article Title: | Ligand-inducible interaction of the DRTP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells |
| Abstract: | Retinoic acid (RA) signaling is mediated by its nuclear receptors RXR and RAR, which bind to their cognate response elements as a heterodimer, RXR/RAR, and act in concert with coregulatory factors to regulate gene transcription on ligand binding. To identify specific cofactors that interact with the RXR/RAR heterodimer in acute promyelocytic leukemia (APL) cells, a double cistronic construct was used that allowed coexpression of the RXR LED (ligand binding domain) with the RAR LED as an affinity matrix to pull dawn interacting proteins from nuclear extracts prepared from a human APL cell line, NB4, A group of proteins was detected whose interaction with RXR/RAR is ligand inducible. The molecular weight pattern of these proteins is similar to that of a complex of proteins previously identified as DRIP or TRAP, which are ligand-dependent transcription activators of VDR and TR, respectively. The RXR/RAR-interacting proteins from NB4 were confirmed to be identical to the DRIP subunits by comparative electrophoresis, Western blot analysis, and in vitro protein interaction assay. In addition to RXR/RAR, the DRIP component can interact directly with the APL-specific PML-RAR alpha fusion protein. The same DRIP complex is present in RA-resistant APL cells and in a variety of cancer cell lines, supporting its global role in transcriptional regulation. (Blood, 2000;96:2233-2239) (C) 2000 by The American Society of Hematology. |
| Keywords: | nuclear receptors; transcriptional activation; transgenic mice; estrogen-receptor; domain; binding; thyroid-hormone receptor; pml-rar-alpha; pml/rar-alpha; histone acetyltransferase; activation function af-2 |
| Journal Title: | Blood |
| Volume: | 96 |
| Issue: | 6 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2000-09-15 |
| Start Page: | 2233 |
| End Page: | 2239 |
| Language: | English |
| ACCESSION: | WOS:000089578000031 |
| PROVIDER: | wos |
| PUBMED: | 10979971 |
| DOI: | 10.1182/blood.V96.6.2233 |
| Notes: | Article -- Source: Wos |
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