Nucleocytoplasmic shuttling of STAT transcription factors.

The signal transducer and activator of transcription (STAT) proteins have initially been described as cytoplasmic proteins that enter the nucleus only after cytokine treatment of cells. Contrary to this assumption, it was demonstrated that STATs are constantly shuttling between nucleus and cytoplasm irrespective of cytokine stimulation. This happens both via carrier-dependent as well as carrier-independent transportation. Moreover, it was also recognized that cytokine stimulation triggers nuclear retention of dimeric STATs, rather than affecting the rate of nuclear import. In summary, it is increasingly being appreciated that STAT nucleocytoplasmic cycling determines the quality of cytokine signaling and also constitutes an important area for microbial intervention.

[1]  C. Horvath.  Weapons of STAT destruction , 2004 .

[2]  Andreas Marg,et al.  Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1 , 2004, The Journal of cell biology.

[3]  A. García-Sastre,et al.  Nipah Virus V and W Proteins Have a Common STAT1-Binding Domain yet Inhibit STAT1 Activation from the Cytoplasmic and Nuclear Compartments, Respectively , 2004, Journal of Virology.

[4]  U. Vinkemeier,et al.  A Single Residue Modulates Tyrosine Dephosphorylation, Oligomerization, and Nuclear Accumulation of Stat Transcription Factors* , 2004, Journal of Biological Chemistry.

[5]  P. Heinrich,et al.  Real Time Analysis of STAT3 Nucleocytoplasmic Shuttling* , 2004, Journal of Biological Chemistry.

[6]  U. Aebi,et al.  The nuclear pore complex: a jack of all trades? , 2004, Trends in biochemical sciences.

[7]  Jian Kang,et al.  Impairment of IL-12-Dependent STAT4 Nuclear Translocation in a Patient with Recurrent Mycobacterium avium Infection1 , 2004, The Journal of Immunology.

[8]  D. Fremont,et al.  N-domain–dependent nonphosphorylated STAT4 dimers required for cytokine-driven activation , 2004, Nature Immunology.

[9]  M. Magnasco,et al.  Virtual gating and nuclear transport: the hole picture. , 2003, Trends in cell biology.

[10]  C. Horvath,et al.  Hendra Virus V Protein Inhibits Interferon Signaling by Preventing STAT1 and STAT2 Nuclear Accumulation , 2003, Journal of Virology.

[11]  K. Shuai,et al.  Regulation of JAK–STAT signalling in the immune system , 2003, Nature Reviews Immunology.

[12]  J. Darnell,et al.  STAT3-dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the alpha 2-macroglobulin gene. , 2003, Genes & development.

[13]  Andreas Marg,et al.  DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1. , 2003, Genes & development.

[14]  Jing Ma,et al.  A Novel Sequence in the Coiled-coil Domain of Stat3 Essential for Its Nuclear Translocation* , 2003, Journal of Biological Chemistry.

[15]  L. Kinnunen,et al.  Importin α Nuclear Localization Signal Binding Sites for STAT1, STAT2, and Influenza A Virus Nucleoprotein* , 2003, Journal of Biological Chemistry.

[16]  Jeffrey G. Williams,et al.  The Dictyostelium prestalk cell inducer DIF regulates nuclear accumulation of a STAT protein by controlling its rate of export from the nucleus , 2003, Development.

[17]  S. Bhattacharya,et al.  Regulation of Stat3 nuclear export. , 2003, The Journal of clinical investigation.

[18]  J. Timmer,et al.  Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Horvath,et al.  Nipah Virus V Protein Evades Alpha and Gamma Interferons by Preventing STAT1 and STAT2 Activation and Nuclear Accumulation , 2002, Journal of Virology.

[20]  M. Ericksen,et al.  Analysis of the Life Cycle of Stat6 , 2002, The Journal of Biological Chemistry.

[21]  J. Darnell,et al.  Signalling: STATs: transcriptional control and biological impact , 2002, Nature Reviews Molecular Cell Biology.

[22]  L. Kinnunen,et al.  Arginine/Lysine-rich Nuclear Localization Signals Mediate Interactions between Dimeric STATs and Importin α5* , 2002, The Journal of Biological Chemistry.

[23]  J. ten Hoeve,et al.  Identification of a Nuclear Stat1 Protein Tyrosine Phosphatase , 2002, Molecular and Cellular Biology.

[24]  K. Arai,et al.  Stat5B Shuttles Between Cytoplasm and Nucleus in a Cytokine-Dependent and -Independent Manner1 , 2002, The Journal of Immunology.

[25]  Edward Yang,et al.  Dissociation Time from DNA Determines Transcriptional Function in a STAT1 Linker Mutant* , 2002, The Journal of Biological Chemistry.

[26]  Kevin M. McBride,et al.  Regulated nuclear import of the STAT1 transcription factor by direct binding of importin‐α , 2002, The EMBO journal.

[27]  I. Lödige,et al.  Constitutive and IFN‐γ‐induced nuclear import of STAT1 proceed through independent pathways , 2002 .

[28]  I. Kerr,et al.  STAT1 from the cell membrane to the DNA , 2001, The EMBO journal.

[29]  L. Kinnunen,et al.  Arginine/Lysine-rich Structural Element Is Involved in Interferon-induced Nuclear Import of STATs* , 2001, The Journal of Biological Chemistry.

[30]  Kevin M. McBride,et al.  Nuclear export signal located within the DNA‐binding domain of the STAT1transcription factor , 2000, The EMBO journal.

[31]  Jeffrey G. Williams,et al.  Glycogen synthase kinase‐3 enhances nuclear export of a Dictyostelium STAT protein , 2000, The EMBO journal.

[32]  U. Vinkemeier,et al.  Nucleocytoplasmic translocation of Stat1 is regulated by a leucine-rich export signal in the coiled-coil domain. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Stark,et al.  How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene , 2000, The EMBO journal.

[34]  P. Heinrich,et al.  Cytoplasmic STAT proteins associate prior to activation. , 2000, The Biochemical journal.

[35]  V. Fried,et al.  Cellular Physiology of STAT3: Where’s the Cytoplasmic Monomer?* , 1999, The Journal of Biological Chemistry.

[36]  E. Schwoebel,et al.  Ran-dependent Signal-mediated Nuclear Import Does Not Require GTP Hydrolysis by Ran* , 1998, The Journal of Biological Chemistry.

[37]  C. Schindler,et al.  Amino-terminal Signal Transducer and Activator of Transcription (STAT) Domains Regulate Nuclear Translocation and STAT Deactivation* , 1998, The Journal of Biological Chemistry.

[38]  G. Stark,et al.  How cells respond to interferons. , 1998, Annual review of biochemistry.

[39]  T. Hirano,et al.  Extracellular signal‐dependent nuclear import of Stat1 is mediated by nuclear pore‐targeting complex formation with NPI‐1, but not Rch1 , 1997, The EMBO journal.

[40]  N. Imamoto,et al.  Ran-unassisted Nuclear Migration of a 97-kD Component of Nuclear Pore–targeting Complex , 1997, The Journal of cell biology.

[41]  T. Hirano,et al.  Interferon-γ-dependent Nuclear Import of Stat1 Is Mediated by the GTPase Activity of Ran/TC4* , 1996, The Journal of Biological Chemistry.

[42]  J. Darnell,et al.  Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex , 1996, Molecular and cellular biology.

[43]  J. Darnell,et al.  The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. , 1996, The EMBO journal.

[44]  B. Chait,et al.  DNA binding of in vitro activated Stat1 alpha, Stat1 beta and truncated Stat1: interaction between NH2‐terminal domains stabilizes binding of two dimers to tandem DNA sites. , 1996, The EMBO journal.

[45]  Tom Maniatis,et al.  Regulation of Interferon-γ-Activated STAT1 by the Ubiquitin-Proteasome Pathway , 1996, Science.

[46]  K. Shuai,et al.  Enhancement of antiproliferative activity of gamma interferon by the specific inhibition of tyrosine dephosphorylation of Stat1 , 1996, Molecular and cellular biology.

[47]  J. Darnell,et al.  A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. , 1995, Genes & development.

[48]  J. Darnell,et al.  Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions , 1994, Cell.

[49]  J. Darnell,et al.  A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. , 1993, Science.

[50]  J. Darnell,et al.  Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. , 1992, Science.

[51]  S. Adam,et al.  Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors , 1990, The Journal of cell biology.

[52]  P. L. Paine,et al.  Nucleocytoplasmic exchange of macromolecules. , 1972, Experimental cell research.

[53]  F. Bischoff,et al.  How Ran is regulated. , 2002, Results and problems in cell differentiation.

[54]  U. Vinkemeier,et al.  Cell type-specific and tyrosine phosphorylation-independent nuclear presence of STAT1 and STAT3. , 2002, Experimental cell research.

[55]  I. Mattaj,et al.  Nucleocytoplasmic transport: the soluble phase. , 1998, Annual review of biochemistry.