RXRα acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells
| Autor: | Ming-Qing Zhang, Hai-Ying Zhou, Sheng-Cai Lin, Chao-Yi Yang, Hang-Zhi Chen, Qiao Wu, Bi-xing Zhao, Xiao-Feng Ye, Xiao-Feng Lin |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytoplasm
Receptors Steroid medicine.drug_class Green Fluorescent Proteins Active Transport Cell Nucleus Retinoic acid Down-Regulation Apoptosis Tretinoin Retinoid X receptor Biology Mice chemistry.chemical_compound Stomach Neoplasms Nuclear Receptor Subfamily 4 Group A Member 1 medicine Animals Humans Retinoid Nuclear pore Receptor Nuclear export signal Alitretinoin Cell Nucleus Orphan receptor Receptors Thyroid Hormone Retinoid X Receptor alpha Thyroid hormone receptor 3T3 Cells Cell Biology Oligonucleotides Antisense Mitochondria Cell biology DNA-Binding Proteins Protein Transport Biochemistry chemistry Nuclear Pore RNA Interference HeLa Cells |
| Zdroj: | Journal of Cell Science. 117:5609-5621 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Retinoid X receptor (RXR) plays a crucial role in the cross talk between retinoid receptors and other hormone receptors including the orphan receptor TR3, forming different heterodimers that transduce diverse steroid/thyroid hormone signaling. Here we show that RXRalpha exhibits nucleocytoplasmic shuttling in MGC80-3 gastric cancer cells and that RXRalpha shuttling is 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 retinoic acid, RXRalpha was almost exclusively located in the cytoplasm. More importantly, we also show that RXRalpha acts as a carrier to assist translocation of TR3, which plays an important role in apoptosis. Both RXRalpha and TR3 colocalized in the nucleus; however, upon stimulation by 9-cis retinoic acid they cotranslocated to the cytoplasm and then localized in the mitochondria. TR3 export depends on RXRalpha, 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 RXRalpha was exported out of the nucleus in response to 9-cis retinoic acid. Moreover, specific reduction of RXRalpha levels caused by anti-sense RXRalpha abolished TR3 nuclear export. In contrast, specific knockdown of TR3 by antisense-TR3 or TR3-siRNA did not affect RXRalpha shuttling. These results indicate that RXRalpha is responsible for TR3 nucleocytoplasmic translocation, which is facilitated by the RXRalpha ligand 9-cis retinoic acid. In addition, mitochondrial TR3, but not RXRalpha, was critical for apoptosis, as TR3 mutants that were distributed in the mitochondria induced apoptosis in the presence or absence of 9-cis retinoic acid. These data reveal a novel aspect of RXRalpha function, in which it acts as a carrier for nucleocytoplasmic translocation of orphan receptors. |
| Databáze: | OpenAIRE |
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