Ligand-inducible interaction of the DRTP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells

Citation
Wl. Shao et al., Ligand-inducible interaction of the DRTP/TRAP coactivator complex with retinoid receptors in retinoic acid-sensitive and -resistant acute promyelocytic leukemia cells, BLOOD, 96(6), 2000, pp. 2233-2239
Citations number
78
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
96
Issue
6
Year of publication
2000
Pages
2233 - 2239
Database
ISI
SICI code
0006-4971(20000915)96:6<2233:LIOTDC>2.0.ZU;2-Q
Abstract
Retinoic acid (RA) signaling is mediated by its nuclear receptors RXR and R AR, which bind to their cognate response elements as a heterodimer, RXR/RAR , and act in concert with coregulatory factors to regulate gene transcripti on 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 (liga nd binding domain) with the RAR LED as an affinity matrix to pull dawn inte racting proteins from nuclear extracts prepared from a human APL cell line, NB4, A group of proteins was detected whose interaction with RXR/RAR is li gand inducible. The molecular weight pattern of these proteins is similar t o that of a complex of proteins previously identified as DRIP or TRAP, whic h 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 c omponent can interact directly with the APL-specific PML-RAR alpha fusion p rotein. The same DRIP complex is present in RA-resistant APL cells and in a variety of cancer cell lines, supporting its global role in transcriptiona l regulation. (Blood, 2000;96:2233-2239) (C) 2000 by The American Society o f Hematology.