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