A Novel Function Of RXRα

Retinoids,a natural or synthetic vitamin A derivative,plays an important role in regulating a broad range of biological processes including cell proliferation, differentiation and apoptosis through its receptors RARs (retinoic acid receptors) and RXRs (retinoid X receptors). RXR forms homodimer itself or heterodimers with other receptors including the orphan receptor TR3. TR3 is a product of immediate-early response gene whose ligand is unknown. When cells are stimulated by apoptosis factors, TR3 is induced rapidly and then translocates from the nucleus to the cytoplasm, in which it targets to the mitochondria,inducing apoptosis.In the present study,we showed that RXRαexhibited nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRαshuttling was energy-dependent through a nuclear pore complex (NPC)-mediated pathway for its import and an intact DNA binding domain-mediated pathway for its export. In the presence of its ligand 9-cis tetinoic acid, RXRαwas almost exclusively located in the cytoplasm. More importantly, we also showed that RXRαacted as a carrier to assist translocation of TR3. Both RXRαand TR3 colocalized in the nucleus and they could form heterodimers; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depended on RXRα, as in living cells GFP-TR3 alone did not result in export from the nucleus even in the presence of 9-cis retinoic acid, whereas GFP-TR3 cotransfected with RXRαwas exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRαlevels caused by anti-sense RXRα...