Interferon γ is recognised by importin α/β: Enhanced nuclear localising and transactivation activities of an interferon γ mimetic

Interferon (IFN) γ’s ability to localise in the nucleus and function in gene activation has been known for some time, although the role of the conventional nuclear transporting importin molecules is unclear. Here, we demonstrate for the first time the direct recognition of IFNγ and an IFNγ mimetic peptide by IMPα and the IMPα/β heterodimer, where the IFNγ mimetic shows higher affinity. Significantly, this correlates well both with in vivo ability to target green fluorescent protein to the nucleus in transfected cells as determined by quantitative confocal laser scanning microscopy, as well as GAS promoter activity of a luciferase reporter. This has important implications for IFNγ’s anti-viral action, and the potential use of the IFNγ mimetic in antiviral therapies.Structured summaryMINT-6478573, MINT-6478550, MINT-6478516:IFN gamma (uniprotkb:P01580) directly interacts (MI:0407) with IMP beta (uniprotkb:Q6GTI5) and IMP alpha (uniprotkb:P52293) by enzyme linked immunosorbent assay (MI:0411)MINT-6478503, MINT-6478490:IFN gamma (uniprotkb:P01580) directly interacts (MI:0407) with IMP alpha (uniprotkb:P52293) by enzyme linked immunosorbent assay (MI:0411)MINT-6478601:T-ag (uniprotkb:P03070) directly interacts (MI:0407) with IMP beta (uniprotkb:Q6GTI5) and IMP alpha (uniprotkb:P52293) by enzyme linked immunosorbent assay (MI:0411)MINT-6478541:T-ag (uniprotkb:P03070) directly interacts (MI:0407) with IMP alpha (uniprotkb:P52293) by enzyme linked immunosorbent assay (MI:0411)