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

Fulcher, Alex J.; Ahmed, Chulbul M.I.; Noon-Song, Ezra N.; Kwan, Rain Y.Q.; Subramaniam, Prem S.; Johnson, Howard M.; Jans, David A.

doi:10.1016/j.febslet.2008.03.054

« Previous Next »FEBS Letters
Volume 582, Issue 11 , Pages 1569-1574, 14 May 2008

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

Edited by Gianni Cesareni

Alex J. Fulcher
- Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, P.O. Box 13D, Victoria, Clayton 3800, Australia
- These authors contributed equally to this manuscript.
Chulbul M.I. Ahmed
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
- These authors contributed equally to this manuscript.
Ezra N. Noon-Song
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
Rain Y.Q. Kwan
- Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, P.O. Box 13D, Victoria, Clayton 3800, Australia
Prem S. Subramaniam
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
Howard M. Johnson
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
- These authors contributed equally to this manuscript.
David A. Jans
- Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, P.O. Box 13D, Victoria, Clayton 3800, Australia
- ARC Centre of Excellence for Biotechnology and Development, Australia
- Corresponding author. Address: Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, P.O. Box 13D, Victoria, Clayton, Australia. Fax: +613 9905 3726.
- These authors contributed equally to this manuscript.

Received 1 February 2008; received in revised form 4 March 2008; accepted 7 March 2008. published online 10 April 2008.

Abstract

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 summary

MINT-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)

Keywords: Interferon gamma, Importin, Nuclear protein import, GAS promoter activity, Confocal laser scanning microscopy