TY - JOUR
T1 - Characterization of receptor-interacting protein 140 in retinoid receptor activities
AU - Lee, Chih Hao
AU - Wei, Li-Na
PY - 1999/10/29
Y1 - 1999/10/29
N2 - Receptor-interacting protein 140 (RIP140) contains multiple receptor interaction domains and interacts with retinoic acid receptors in a ligand- dependent manner. Nine LXXLL receptor-interacting motifs are organized into two clusters within this molecule, each differentially interacting with retinoic acid receptor (RAR) and retinoid X receptor (RXR). RAR interacts with the 5' cluster, whereas RXR interacts with both clusters. Additionally, a third ligand-dependent receptor-interacting domain is assigned to the very C terminus of this molecule, which contains no LXXL motif. In mammalian cells, receptor heterodimerization is required for efficient interaction of RAR/RXR with RIP140. Furthermore, the heterodimeric, holoreceptors cooperatively interact with RIP140, which requires the activation function 2 domains of both receptors. By using different retinoic acid reporter systems, it is demonstrated that RIP140 strongly suppresses retinoic acid induction of reporter activities, but coactivator SRC-1 enhances it. Furthermore, an intrinsic repressive activity of RIP140 is demonstrated in a GAL4 fusion system. Unlike receptor corepressor, which interacts with antagonist-bound RAR/RXRs, RIP140 does not interact with antagonist-occupied RAR/RXR dimers. These data suggest that RIP140 represents a third coregulator category that is able to suppress the activation of certain agonist-bound hormone receptors.
AB - Receptor-interacting protein 140 (RIP140) contains multiple receptor interaction domains and interacts with retinoic acid receptors in a ligand- dependent manner. Nine LXXLL receptor-interacting motifs are organized into two clusters within this molecule, each differentially interacting with retinoic acid receptor (RAR) and retinoid X receptor (RXR). RAR interacts with the 5' cluster, whereas RXR interacts with both clusters. Additionally, a third ligand-dependent receptor-interacting domain is assigned to the very C terminus of this molecule, which contains no LXXL motif. In mammalian cells, receptor heterodimerization is required for efficient interaction of RAR/RXR with RIP140. Furthermore, the heterodimeric, holoreceptors cooperatively interact with RIP140, which requires the activation function 2 domains of both receptors. By using different retinoic acid reporter systems, it is demonstrated that RIP140 strongly suppresses retinoic acid induction of reporter activities, but coactivator SRC-1 enhances it. Furthermore, an intrinsic repressive activity of RIP140 is demonstrated in a GAL4 fusion system. Unlike receptor corepressor, which interacts with antagonist-bound RAR/RXRs, RIP140 does not interact with antagonist-occupied RAR/RXR dimers. These data suggest that RIP140 represents a third coregulator category that is able to suppress the activation of certain agonist-bound hormone receptors.
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U2 - 10.1074/jbc.274.44.31320
DO - 10.1074/jbc.274.44.31320
M3 - Article
C2 - 10531331
AN - SCOPUS:0033615549
SN - 0021-9258
VL - 274
SP - 31320
EP - 31326
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -