Modulation of STAT signaling by STAT-interacting proteins

STATs (signal transducer and activator of transcription) play important roles in numerous cellular processes including immune responses, cell growth and differentiation, cell survival and apoptosis, and oncogenesis. In contrast to many other cellular signaling cascades, the STAT pathway is direct: STATs bind to receptors at the cell surface and translocate into the nucleus where they function as transcription factors to trigger gene activation. However, STATs do not act alone. A number of proteins are found to be associated with STATs. These STAT-interacting proteins function to modulate STAT signaling at various steps and mediate the crosstalk of STATs with other cellular signaling pathways. This article reviews the roles of STAT-interacting proteins in the regulation of STAT signaling.

[1]  B. Groner,et al.  Characterization of Stat5a and Stat5b Homodimers and Heterodimers and Their Association with the Glucocortiocoid Receptor in Mammary Cells , 1998, Molecular and Cellular Biology.

[2]  L. Naumovski,et al.  Subcellular localization of interferon-inducible Myc/stat-interacting protein Nmi is regulated by a novel IFP 35 homologous domain. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[3]  J. Darnell STATs and gene regulation. , 1997, Science.

[4]  R. Aebersold,et al.  Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins , 1992, Molecular and cellular biology.

[5]  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.

[6]  P Jay,et al.  Specific inhibition of Stat3 signal transduction by PIAS3. , 1997, Science.

[7]  S. Bell,et al.  Initiation of DNA replication in eukaryotic cells. , 1997, Annual review of cell and developmental biology.

[8]  Richard J Smeyne,et al.  Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements , 1995, Neuron.

[9]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[10]  Dwight C. Look,et al.  Stat1 Depends on Transcriptional Synergy with Sp1 (*) , 1995, The Journal of Biological Chemistry.

[11]  S. Hyman,et al.  Coordinate Regulation of Choline Acetyltransferase, Tyrosine Hydroxylase, and Neuropeptide mRNAs by Ciliary Neurotrophic Factor and Leukemia Inhibitory Factor in Cultured Sympathetic Neurons , 1994, Journal of neurochemistry.

[12]  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.

[13]  C. Glass,et al.  Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Hamil,et al.  Protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1) is a nuclear receptor coregulator expressed in human testis. , 2000, Molecular endocrinology.

[15]  T. Decker,et al.  Cytoplasmic activation of GAF, an IFN‐gamma‐regulated DNA‐binding factor. , 1991, The EMBO journal.

[16]  Y. Yoneda,et al.  Nuclear import and export of proteins: the molecular basis for intracellular signaling. , 1998, Cytokine & growth factor reviews.

[17]  Tony J. Pircher,et al.  Mitogen-activated protein kinase kinase inhibition decreases growth hormone stimulated transcription mediated by STAT5 , 1997, Molecular and Cellular Endocrinology.

[18]  J A Gustafsson,et al.  Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a. , 1999, Molecular endocrinology.

[19]  David M. Heery,et al.  A signature motif in transcriptional co-activators mediates binding to nuclear receptors , 1997, Nature.

[20]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[21]  B. Valdez,et al.  Cloning and characterization of Gu/RH-II binding protein. , 1997, Biochemical and biophysical research communications.

[22]  L. Sanders,et al.  Functional differences between Stat3alpha and Stat3beta , 1997, Molecular and cellular biology.

[23]  H. Hauser,et al.  Dynamic redistribution of STAT1 protein in IFN signaling visualized by GFP fusion proteins. , 1999, European journal of biochemistry.

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

[25]  B. Groner,et al.  Functional interactions between Stat5 and the glucocorticoid receptor , 1996, Nature.

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

[27]  R. Aebersold,et al.  The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Chang,et al.  Inhibition of Stat1-mediated gene activation by PIAS1. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Baeuerle,et al.  IKAP is a scaffold protein of the IκB kinase complex , 1998, Nature.

[30]  R. Aebersold,et al.  Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Toppari,et al.  A Testis-specific Androgen Receptor Coregulator That Belongs to a Novel Family of Nuclear Proteins* , 1999, The Journal of Biological Chemistry.

[32]  G. Lyons,et al.  Miz1, a novel zinc finger transcription factor that interacts with Msx2 and enhances its affinity for DNA , 1997, Mechanisms of Development.

[33]  C. Glass,et al.  Co-activators and co-repressors in the integration of transcriptional responses. , 1998, Current opinion in cell biology.

[34]  Miguel Beato,et al.  Steroid hormone receptors: Many Actors in search of a plot , 1995, Cell.

[35]  W. Leonard,et al.  Functional Association of Nmi with Stat5 and Stat1 in IL-2- and IFN γ-Mediated Signaling , 1999, Cell.

[36]  J. Yasuda,et al.  A mammalian scaffold complex that selectively mediates MAP kinase activation. , 1998, Science.

[37]  E. Korzus,et al.  The Mitogen-activated Protein Kinase and JAK-STAT Signaling Pathways Are Required for an Oncostatin M-responsive Element-mediated Activation of Matrix Metalloproteinase 1 Gene Expression* , 1997, The Journal of Biological Chemistry.

[38]  B. Chait,et al.  Ser727‐dependent recruitment of MCM5 by Stat1α in IFN‐γ‐induced transcriptional activation , 1998 .

[39]  D. Levy The house that Jak/Stat built. , 1997, Cytokine & growth factor reviews.

[40]  N. Reich,et al.  Distinct STAT Structure Promotes Interaction of STAT2 with the p48 Subunit of the Interferon-α-stimulated Transcription Factor ISGF3* , 1997, The Journal of Biological Chemistry.

[41]  B. Groner,et al.  Beta-casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor , 1991, Molecular and cellular biology.

[42]  Christopher K. Glass,et al.  The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function , 1997, Nature.

[43]  S. Mohr,et al.  Zimp encodes a homologue of mouse Miz1 and PIAS3 and is an essential gene in Drosophila melanogaster. , 1999, Gene.

[44]  J. Darnell,et al.  Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. , 1992, Science.

[45]  J. Darnell,et al.  ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[46]  J. Darnell,et al.  Crystal Structure of a Tyrosine Phosphorylated STAT-1 Dimer Bound to DNA , 1998, Cell.

[47]  S. Bhattacharya,et al.  Cooperation of Stat2 and p300/CBP in signalling induced by interferon-α , 1996, Nature.

[48]  S. Becker,et al.  Three-dimensional structure of the Stat3β homodimer bound to DNA , 1998, Nature.

[49]  J. Darnell,et al.  Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation , 1995, Cell.

[50]  Peter F. Johnson,et al.  Interleukin-6-Specific Activation of the C/EBPδ Gene in Hepatocytes Is Mediated by Stat3 and Sp1 , 1998, Molecular and Cellular Biology.

[51]  T. Ito,et al.  Nuclear factors interacting with an interleukin-6 responsive element of rat alpha 2-macroglobulin gene. , 1989, Nucleic acids research.

[52]  M. Schwab,et al.  Nmi protein interacts with regions that differ between MycN and Myc and is localized in the cytoplasm of neuroblastoma cells in contrast to nuclear MycN , 1999, Oncogene.

[53]  L. Naumovski,et al.  Interferon-induced upregulation and cytoplasmic localization of Myc-interacting protein Nmi. , 1998, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

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

[55]  J. Darnell,et al.  Interacting Regions in Stat3 and c-Jun That Participate in Cooperative Transcriptional Activation , 1999, Molecular and Cellular Biology.

[56]  J E Darnell,et al.  A nuclear protein tyrosine phosphatase is required for the inactivation of Stat1. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. Darnell,et al.  Two contact regions between Stat1 and CBP/p300 in interferon γ signaling , 1996 .

[58]  J. T. Kadonaga Eukaryotic Transcription: An Interlaced Network of Transcription Factors and Chromatin-Modifying Machines , 1998, Cell.

[59]  J. Rosen,et al.  Glucocorticoid receptor/signal transducer and activator of transcription 5 (STAT5) interactions enhance STAT5 activation by prolonging STAT5 DNA binding and tyrosine phosphorylation. , 1999, Molecular endocrinology.

[60]  K. Shuai The STAT family of proteins in cytokine signaling. , 1999, Progress in biophysics and molecular biology.

[61]  L. Sanders,et al.  Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. , 1995, Proceedings of the National Academy of Sciences of the United States of America.