Molecular pathways involved in the transport of nuclear receptors from the nucleus to cytoplasm

Nuclear receptors (NRs) are transcription regulators that direct the expression of many genes linked to cellular processes, such as proliferation, differentiation, and apoptosis. Additionally, some cellular events are also modulated by signaling pathways induced by NRs outside of the nucleus. Hence, the subcellular transport of NRs is dynamic and is modulated by several signals, protein-protein interactions, and posttranslational modifications. Particularly, the exit of NRs from the nucleus to cytoplasm and/or other compartments is transcendental, as it is this export event, which determines their abundance in the cells' compartments, the activation or attenuation of nuclear or extranuclear pathways, and the magnitude and duration of their effects inside or outside of the nucleus. Consequently, an adequate control of the distribution of NRs is critical for homeostasis, because a deregulation in the nucleo-cytoplasmic transport of NRs could be involved in diseases including cancer as well as metabolic and vascular alterations. In this review, we investigated the pathways and molecular and biological aspects that have been described for the nuclear export of NRs so far and their functional relevance in some diseases. This information suggests that the transport of NRs out of the nucleus is a key mechanism for the identification of new therapeutic targets for alterations associated with the deregulation of the function of NRs.