Interferon gamma is recognised by importin alpha/beta: enhanced nuclear localising and transactivation activities of an interferon gamma mimetic.
Interferon (IFN) gamma'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 IFNgamma and an IFNgamma mimetic peptide by IMPalpha and the IMPalpha/beta heterodimer, where the IFNgamma 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 IFNgamma's anti-viral action, and the potential use of the IFNgamma mimetic in antiviral therapies.
Fulcher
Alex J
AJ
Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, P.O. Box 13D, Victoria, Clayton 3800, Australia.
Ahmed
Chulbul M I
CM
Noon-Song
Ezra N
EN
Kwan
Rain Y Q
RY
Subramaniam
Prem S
PS
Johnson
Howard M
HM
Jans
David A
DA
D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000378:metabolism; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D010455:Peptides; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D028901:alpha Karyopherins / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
D019913:Nuclear Localization Signals; D010455:Peptides; D011993:Recombinant Fusion Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma