Fig. 8. Conceptual model of STAT1 nuclear translocation. Latent STAT1 exists in the cytoplasm as a monomer. Following IFN-γ stimulation, STAT1 is tyrosine phosphorylated and dimerizes via intermolecular phosphotyrosine (pY)-SH2 domains. Dimerization results in a conformational change that allows the STAT1 NLS on each monomer to become functional. The importin-α5 (impα) shuttling receptor recognizes and binds to the NLS on the STAT1 dimer and effects translocation into the nucleus in association with importin-β (impβ). In the nucleus, STAT1 recognition of a specific DNA target leads to dissociation of importin-α5. Importin-α5 can be recycled to the cytoplasm by the cellular apoptosis susceptibility protein (CAS) export receptor.