摘要 : IGFBP-3 interacts with the retinoid X receptor-alpha (RXR alpha) and retinoic acid receptor-alpha (RAR alpha) and thereby interferes with the formation of RXR:RAR heterodimers. Here we identify the domains in RXR alpha and IGFBP-3... 展开 IGFBP-3 interacts with the retinoid X receptor-alpha (RXR alpha) and retinoic acid receptor-alpha (RAR alpha) and thereby interferes with the formation of RXR:RAR heterodimers. Here we identify the domains in RXR alpha and IGFBP-3 that participate in this interaction. When different regions of RXR alpha were expressed independently, we found that only the DNA-binding domain (C-domain) bound IGFBP-3. Residues in the second Zn-finger loop (Gln49, Arg52), which contribute to C-domain dimerization on DR1 response elements, proved essential to IGFBP-3 binding. In complementary studies, we found that residues within the N-terminal domain of IGFBP-3 (Thr58, Arg60) and motifs in its C-terminal domain ((220)LysLysLys, (228)LysGlyArgLysArg) were required for interaction with RXR alpha and RAR alpha. Unlike wild-type IGFBP-3, the non-retinoid receptor-binding mutants of IGFBP-3 were unable to attenuate all-trans-retinoic acid-induced transactivation of the RAR response element by RXR:RAR heterodimers. We conclude that residues in both the N- and C-terminal domains of IGFBP-3 are involved in binding the retinoid receptors, and that this interaction is essential to the modulation of RAR-signaling by IGFBP-3. (C) 2007 Elsevier Inc. All rights reserved. 收起