Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-alpha

The EMBO Journal
K M McBrideN C Reich

Abstract

Signal transducers and activators of transcription (STATs) reside in a latent state in the cytoplasm of the cell, but accumulate in the nucleus in response to cytokines or growth factors. Localization in the nucleus occurs following STAT tyrosine phosphorylation and dimerization. In this report we demonstrate a direct interaction of importin-alpha5 with tyrosine-phosphorylated STAT1 dimers, and provide evidence that a nuclear localization signal (NLS) exists in an inactive state within a STAT1 monomer. A mutation in STAT1 leucine 407 (L407A) is characterized, which generates a protein that is accurately tyrosine phosphorylated in response to interferon, dimerizes and binds DNA, but does not localize to the nucleus. The import defect of STAT1(L407A) appears to be a consequence of the inability of this protein to be recognized by its import shuttling receptor. In addition, we demonstrate that STAT1 binding to specific target DNA effectively blocks importin-alpha5 binding. This result may play a role in localizing STAT1 to its destination in the nucleus, and in releasing importin-alpha5 from STAT1 for recycling back to the cytoplasm.

References

Dec 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M J GutchN C Reich
Aug 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·C SchindlerJ E Darnell
Aug 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·X Y FuJ E Darnell
Dec 1, 1991·Trends in Biochemical Sciences·C Dingwall, R A Laskey
Jan 1, 1995·Annual Review of Biochemistry·L I Davis
Jan 1, 1995·Annual Review of Immunology·J N IhleO Silvennoinen
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·P CortesD Baltimore
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·T ImprotaJ E Darnell
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·J MoroianuA Radu
Sep 12, 1997·Science·J E Darnell
May 23, 1998·Annual Review of Immunology·W J Leonard, J J O'Shea
Jun 26, 1998·Current Opinion in Cell Biology·L F PembertonJ S Rosenblum
Jul 31, 1998·Experimental Cell Research·N KudoM Yoshida
Oct 6, 1998·Annual Review of Biochemistry·G R StarkR D Schreiber
Oct 6, 1998·Annual Review of Biochemistry·I W Mattaj, L Englmeier
Nov 7, 1998·The Journal of Biological Chemistry·K Mowen, M David
Feb 13, 1999·The Journal of Biological Chemistry·J HerringtonC Carter-Su
Jul 8, 1999·Current Opinion in Cell Biology·S A Adam
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·R L Haspel, J E Darnell
Dec 28, 1999·Annual Review of Cell and Developmental Biology·D Görlich, U Kutay
Jun 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D A JansM H Lam
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·A BegittU Vinkemeier
Sep 13, 2000·Molecular and Cellular Biology·K Mowen, M David
Oct 20, 2000·The Journal of Biological Chemistry·M R HodelA E Hodel
Jan 11, 2001·The Journal of Biological Chemistry·K MelenI Julkunen
Mar 22, 2001·EMBO Reports·M CokolB Rost
May 22, 2001·Newsline
Dec 1, 2001·Microbiology and Molecular Biology Reviews : MMBR·I G Macara

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Citations

May 12, 2006·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Karine CrozatBruce Beutler
Sep 22, 2005·Breast Cancer Research and Treatment·A CarvajalG I Owen
Jun 6, 2003·Advanced Drug Delivery Reviews·Joshua Z Gasiorowski, David A Dean
Jan 12, 2010·Cell Death and Differentiation·J-C Marine
Mar 28, 2008·Cell Research·Jinbo Yang, George R Stark
Oct 3, 2002·Nature Reviews. Cancer·James E Darnell
Jul 27, 2006·Nature Reviews. Immunology·Nancy C Reich, Ling Liu
Nov 10, 2006·Systems Biology·V Mayya, L M Loew
Mar 9, 2012·The Journal of Biological Chemistry·Jill A FielhaberArnold S Kristof
Dec 27, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Melissa M Brierley, Eleanor N Fish
Aug 22, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Christopher F Basler, Gaya K Amarasinghe
Feb 1, 2008·International Immunology·Ryuta MuromotoTadashi Matsuda
Dec 21, 2004·European Journal of Biochemistry·Thomas Meyer, Uwe Vinkemeier
Nov 6, 2009·Journal of Virology·Mathieu MateoViktor E Volchkov
May 16, 2006·Journal of Virology·St Patrick ReidChristopher F Basler
Aug 8, 2007·Molecular and Cellular Biology·M M PradeepaM R S Rao
May 19, 2010·Molecular and Cellular Biology·Calin-Bogdan ChiribauMaria Hatzoglou
May 18, 2011·Molecular and Cellular Biology·Filipa AntunesUwe Vinkemeier
Feb 20, 2008·Biochemistry. Biokhimii︠a︡·A V SorokinL P Ovchinnikov
May 17, 2011·Cancer Research·Euan A StronachHani Gabra
Apr 1, 2010·BMC Immunology·Astrid SkjesolJorunn B Jørgensen
Dec 25, 2010·Cell Communication and Signaling : CCS·Jonathan D NardozziGino Cingolani
Feb 22, 2014·Annual Review of Immunology·William M SchneiderCharles M Rice
Apr 3, 2014·Science Signaling·David P Doupé, Norbert Perrimon
May 20, 2014·Virchows Archiv : an International Journal of Pathology·Lisa ArztHelmut H Popper
May 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ling LiuNancy C Reich
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Minghao ZhongJames E Darnell
Jan 12, 2007·Molecular BioSystems·Cheh Peng Lim, Xinmin Cao
Mar 10, 2007·FEBS Letters·Surinder M SoondAnastasis Stephanou

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