stat transcription factors

Summary

Summary: A family of transcription factors containing SH2 DOMAINS that are involved in CYTOKINE-mediated SIGNAL TRANSDUCTION. STAT transcription factors are recruited to the cytoplasmic region of CELL SURFACE RECEPTORS and are activated via PHOSPHORYLATION. Once activated they dimerize and translocate into the CELL NUCLEUS where they influence GENE expression. They play a role in regulating CELL GROWTH PROCESSES and CELL DIFFERENTIATION. STAT transcription factors are inhibited by SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS and PROTEIN INHIBITORS OF ACTIVATED STAT.

Top Publications

  1. Dorritie K, McCubrey J, Johnson D. STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia. 2014;28:248-57 pubmed publisher
    ..This review summarizes our current understanding of STAT protein involvement in normal hematopoiesis and leukemogenesis, as well as recent advances in the development and testing of novel STAT inhibitors. ..
  2. Staab J, Barth P, Meyer T. Cell-type-specific expression of STAT transcription factors in tissue samples from patients with lymphocytic thyroiditis. Endocr Pathol. 2012;23:141-50 pubmed publisher
    ..Immunohistochemical analysis demonstrated differential expression patterns of the various members of the STAT transcription factors examined, indicating that each member of this conserved protein family has its distinct functions in the ..
  3. O Shea J, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36:542-50 pubmed publisher
    ..Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease. ..
  4. Rodrigues A, Zoranovic T, Ayala Camargo A, Grewal S, Reyes Robles T, Krasny M, et al. Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis. Development. 2012;139:4051-61 pubmed publisher
    ..As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine. ..
  5. Araki T, Williams J. Perturbations of the actin cytoskeleton activate a Dictyostelium STAT signalling pathway. Eur J Cell Biol. 2012;91:420-5 pubmed publisher
    ..We suggest that PTP3 phosphorylation, and consequent STATc activation, are regulated by changes in F-actin polymerization status during stress and DIF-induced cytoskeletal remodelling. ..
  6. Sansone P, Bromberg J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J Clin Oncol. 2012;30:1005-14 pubmed publisher
  7. Grönholm J, Kaustio M, Myllymäki H, Kallio J, Saarikettu J, Kronhamn J, et al. Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells. FASEB J. 2012;26:1239-50 pubmed publisher
    ..However, Not4 is required for binding of Stat92E to its DNA recognition sequence in the TotM gene promoter. In summary, Not4/CNOT4 is a novel positive regulator of the JAK/STAT pathway in Drosophila and in humans. ..
  8. Wang W, Li Y, Zhou L, Yue H, Luo H. Role of JAK/STAT signaling in neuroepithelial stem cell maintenance and proliferation in the Drosophila optic lobe. Biochem Biophys Res Commun. 2011;410:714-20 pubmed publisher
    ..Thus, in addition to its role in suppression of neuroblast formation, the JAK/STAT pathway is necessary and sufficient for optic lobe neuroepithelial growth. ..
  9. Johnson A, Mokalled M, Haden T, Olson E. JAK/Stat signaling regulates heart precursor diversification in Drosophila. Development. 2011;138:4627-38 pubmed publisher
    ..This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain. ..

More Information

Publications62

  1. Tsurumi A, Xia F, Li J, Larson K, Lafrance R, Li W. STAT is an essential activator of the zygotic genome in the early Drosophila embryo. PLoS Genet. 2011;7:e1002086 pubmed publisher
    ..We further show that STAT92E and Zelda synergistically regulate transcription. We conclude that STAT92E, in conjunction with Zelda, plays an important role in transcription of the zygotic genome at the onset of embryonic development. ..
  2. Zou J, Secombes C. Teleost fish interferons and their role in immunity. Dev Comp Immunol. 2011;35:1376-87 pubmed publisher
  3. Yoon W, Meinhardt H, Montell D. miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. Nat Cell Biol. 2011;13:1062-9 pubmed publisher
    ..Mathematical modelling and simulations of this regulatory circuit including miR-279, Apt and Ken supported key roles for miR-279 and Apt in generating threshold responses to the Upd gradient. ..
  4. Stark G, Darnell J. The JAK-STAT pathway at twenty. Immunity. 2012;36:503-14 pubmed publisher
    ..These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all. ..
  5. Montell D, Yoon W, Starz Gaiano M. Group choreography: mechanisms orchestrating the collective movement of border cells. Nat Rev Mol Cell Biol. 2012;13:631-45 pubmed publisher
    ..Here we provide an overview of the molecular choreography of border cells and its more general implications. ..
  6. Gao B, Wang H, Lafdil F, Feng D. STAT proteins - key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver. J Hepatol. 2012;57:430-41 pubmed publisher
    ..The identification of functions for these STAT proteins has increased our understanding of liver disease pathophysiology and treatments, while also suggesting new therapeutic modalities for managing liver disease. ..
  7. Zhao X, Cheng G, Jiao Y, Yan W, Liu M, Zheng Z. Cloning and characterization of porcine interferon-?-related genes identified by genomic database screening. J Interferon Cytokine Res. 2012;32:378-85 pubmed publisher
    ..The antiviral activity of PoIFN-?-related subtypes varies a lot in different subtypes. Among all the PoIFN-? subtypes detected, PoIFN-?8 has the strongest antiviral and immunomodulatory activities. ..
  8. Vainchenker W, Constantinescu S. JAK/STAT signaling in hematological malignancies. Oncogene. 2013;32:2601-13 pubmed publisher
  9. Yao R, Ma Y, Liang W, Li H, Ma Z, Yu X, et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE. 2012;7:e46082 pubmed publisher
    ..Therefore, we demonstrated that miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by targeting SOCS1. ..
  10. Woodfield S, Graves H, Hernandez J, Bergmann A. De-regulation of JNK and JAK/STAT signaling in ESCRT-II mutant tissues cooperatively contributes to neoplastic tumorigenesis. PLoS ONE. 2013;8:e56021 pubmed publisher
    ..This is the first rigorous study of tissues predominantly mutant for endocytic nTSGs and provides clear evidence for cooperation among de-regulated signaling pathways leading to tumorigenesis. ..
  11. Hayashi Y, Sexton T, Dejima K, Perry D, Takemura M, Kobayashi S, et al. Glypicans regulate JAK/STAT signaling and distribution of the Unpaired morphogen. Development. 2012;139:4162-71 pubmed publisher
    ..Furthermore, we establish the follicular epithelium as a new model for morphogen signaling in complex organ development. ..
  12. Hubackova S, Krejcikova K, Bartek J, Hodny Z. Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells. J Biol Chem. 2012;287:26702-14 pubmed publisher
    ..As IL6 is induced in response to various viral and genotoxic stresses, this cytokine may regulate autocrine/paracrine induction of PML under these pathophysiological states as part of tissue adaptation to local stress. ..
  13. Cokic V, Bhattacharya B, Beleslin Cokic B, Noguchi C, Puri R, Schechter A. JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny. J Transl Med. 2012;10:116 pubmed publisher
  14. Kiu H, Nicholson S. Biology and significance of the JAK/STAT signalling pathways. Growth Factors. 2012;30:88-106 pubmed publisher
    ..While there is still more to learn, we now appreciate how disruption and deregulation of this pathway can result in clinical disease and look forward to adoption of the next generation of JAK inhibitors in routine clinical treatment. ..
  15. Jang A, Chang Y, Bai J, Montell D. Border-cell migration requires integration of spatial and temporal signals by the BTB protein Abrupt. Nat Cell Biol. 2009;11:569-79 pubmed publisher
    ..Taken together, these findings provide a molecular mechanism by which spatial and temporal cues are integrated. ..
  16. Hubackova S, Novakova Z, Krejcikova K, Kosar M, Dobrovolna J, Duskova P, et al. Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling. Cell Cycle. 2010;9:3085-99 pubmed publisher
  17. Classen A, Bunker B, Harvey K, Vaccari T, Bilder D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet. 2009;41:1150-5 pubmed publisher
    ..These findings show that PcG proteins can restrict growth directly by silencing mitogenic signaling pathways, shedding light on an epigenetic mechanism underlying tumor suppression. ..
  18. Gilbert M, Beam C, Robinson B, Moberg K. Genetic interactions between the Drosophila tumor suppressor gene ept and the stat92E transcription factor. PLoS ONE. 2009;4:e7083 pubmed publisher
  19. Quaiser T, Mönnigmann M. Systematic identifiability testing for unambiguous mechanistic modeling--application to JAK-STAT, MAP kinase, and NF-kappaB signaling pathway models. BMC Syst Biol. 2009;3:50 pubmed publisher
    ..We demonstrate how the proposed method can be combined with biological insight, however, to simplify these models. ..
  20. Gutierrez Aviño F, Ferres Marco D, Dominguez M. The position and function of the Notch-mediated eye growth organizer: the roles of JAK/STAT and four-jointed. EMBO Rep. 2009;10:1051-8 pubmed publisher
    ..These findings redefine the process of organizer formation and function, and they identify four-jointed as a regulatory node, integrating multiple growth-control pathways. ..
  21. Plumlee C, Lee C, Beg A, Decker T, Shuman H, Schindler C. Interferons direct an effective innate response to Legionella pneumophila infection. J Biol Chem. 2009;284:30058-66 pubmed publisher
    ..pneumophila. Surprisingly, this suppression is mediated by a pathway that is independent of Stat1, Stat2, Stat3, but correlates with the polarization of macrophages toward the M1 or classically activated phenotype. ..
  22. Starz Gaiano M, Melani M, Meinhardt H, Montell D. Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells. Cell Cycle. 2009;8:2917-25 pubmed
    ..By combining biological experiments and mathematical modeling, we can achieve a more sophisticated understanding of how cells interpret molecular gradients. ..
  23. O Shea J, Lahesmaa R, Vahedi G, Laurence A, Kanno Y. Genomic views of STAT function in CD4+ T helper cell differentiation. Nat Rev Immunol. 2011;11:239-50 pubmed publisher
    ..Defining exactly how extrinsic signals control the specification and plasticity of T(H) cells will provide important insights and perhaps therapeutic opportunities in these diseases. ..
  24. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798-809 pubmed publisher
    ..Consequently, STAT3 is a promising target to redirect inflammation for cancer therapy. ..
  25. Wright V, Vogt K, Smythe E, Zeidler M. Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cell Signal. 2011;23:920-7 pubmed publisher
    ..Finally, investigations into the effects of ectopic expression of Upd3 in vivo have confirmed its ability to activate pathway signalling at long-distance...
  26. Kallio J, Myllymäki H, Grönholm J, Armstrong M, Vanha aho L, Mäkinen L, et al. Eye transformer is a negative regulator of Drosophila JAK/STAT signaling. FASEB J. 2010;24:4467-79 pubmed publisher
    ..In conclusion, we have identified ET as a novel negative regulator of the Drosophila JAK/STAT pathway both in vitro and in vivo, and it functions in regulating Stat92E phosphorylation. ..
  27. Flaherty M, Salis P, Evans C, Ekas L, Marouf A, Zavadil J, et al. chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila. Dev Cell. 2010;18:556-68 pubmed publisher
    ..Like hyperactivated Stat92E, Chinmo misexpression in CySCs is sufficient to maintain GSCs nonautonomously. Chinmo is therefore a key effector of JAK/STAT signaling in a variety of developmental and pathological contexts. ..
  28. Stofanko M, Kwon S, Badenhorst P. Lineage tracing of lamellocytes demonstrates Drosophila macrophage plasticity. PLoS ONE. 2010;5:e14051 pubmed publisher
    ..Taken together, our data suggest that lamellocytes arise from plasmatocytes and that plasmatocytes may be inherently plastic, possessing the ability to differentiate further into lamellocytes upon appropriate challenge. ..
  29. Liu W, Singh S, Hou S. JAK-STAT is restrained by Notch to control cell proliferation of the Drosophila intestinal stem cells. J Cell Biochem. 2010;109:992-9 pubmed publisher
    ..This study provides insight into how stem cells, under steady conditions, balance the processes of proliferation and differentiation to maintain the stable cellular composition of a healthy tissue. ..
  30. Souza Neto J, Sim S, Dimopoulos G. An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci U S A. 2009;106:17841-6 pubmed publisher
    ..Our data suggest that the JAK-STAT pathway is part of the A. aegypti mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses. ..
  31. Jiang H, Patel P, Kohlmaier A, Grenley M, McEwen D, Edgar B. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;137:1343-55 pubmed publisher
    ..Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis. ..
  32. Sheng X, Brawley C, MATUNIS E. Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis. Cell Stem Cell. 2009;5:191-203 pubmed publisher
  33. Benekli M, Baumann H, Wetzler M. Targeting signal transducer and activator of transcription signaling pathway in leukemias. J Clin Oncol. 2009;27:4422-32 pubmed publisher
    ..Mechanisms of STAT activation, the potential role of STAT signaling in leukemogenesis, and recent advances in drug discovery targeting the STAT pathway are the focus of this review. ..
  34. Wang Y, Huang M. Organogenesis and tumorigenesis: insight from the JAK/STAT pathway in the Drosophila eye. Dev Dyn. 2010;239:2522-33 pubmed publisher
    ..In this review, we focus on the functions and regulation of the JAK/STAT pathway during eye development and provide some insights into the study of this pathway in tumorigenesis. ..
  35. Silver J, Hunter C. gp130 at the nexus of inflammation, autoimmunity, and cancer. J Leukoc Biol. 2010;88:1145-56 pubmed publisher
    ..The aim of this review is to discuss the role of gp130 in promoting or preventing the development of autoimmunity and cancer, two processes that are associated with aberrant inflammatory responses. ..
  36. Goto A, Yano T, Terashima J, Iwashita S, Oshima Y, Kurata S. Cooperative regulation of the induction of the novel antibacterial Listericin by peptidoglycan recognition protein LE and the JAK-STAT pathway. J Biol Chem. 2010;285:15731-8 pubmed publisher
    ..Based on these findings, we propose that the Listericin gene encodes a novel antibacterial peptide-like protein whose induction is cooperatively regulated by PGRP-LE and the JAK-STAT pathway. ..
  37. Ortiz Muñoz G, Lopez Parra V, Lopez Franco O, Fernandez Vizarra P, Mallavia B, Flores C, et al. Suppressors of cytokine signaling abrogate diabetic nephropathy. J Am Soc Nephrol. 2010;21:763-72 pubmed publisher
    ..Suppression of the JAK/STAT pathway by increasing intracellular SOCS proteins may have therapeutic potential in diabetic nephropathy. ..
  38. Flaherty M, Zavadil J, Ekas L, Bach E. Genome-wide expression profiling in the Drosophila eye reveals unexpected repression of notch signaling by the JAK/STAT pathway. Dev Dyn. 2009;238:2235-53 pubmed publisher
    ..These data suggest that this study will be a useful resource for the identification of additional Stat92E targets. ..
  39. Gupta L, Molina Cruz A, Kumar S, Rodrigues J, Dixit R, Zamora R, et al. The STAT pathway mediates late-phase immunity against Plasmodium in the mosquito Anopheles gambiae. Cell Host Microbe. 2009;5:498-507 pubmed publisher
    ..Chemical inhibition of mosquito NOS activity after oocyte formation increases oocyte survival. Thus, the AgSTAT-A pathway mediates a late-phase antiplasmodial response that reduces oocyst survival in A. gambiae. ..
  40. Adamson A, Collins K, Laurence A, O Shea J. The Current STATus of lymphocyte signaling: new roles for old players. Curr Opin Immunol. 2009;21:161-6 pubmed publisher
    ..Focusing on how STATs work in concert with other transcription factors will hopefully provide a better mechanistic understanding of the pathogenesis of various autoimmune diseases. ..
  41. Singh S, Zheng Z, Wang H, Oh S, Chen X, Hou S. Competitiveness for the niche and mutual dependence of the germline and somatic stem cells in the Drosophila testis are regulated by the JAK/STAT signaling. J Cell Physiol. 2010;223:500-10 pubmed publisher
    ..These data suggest that a single JAK/STAT signal from the niche orchestrate the competitive and dependent co-existence of GSCs and CPCs in the Drosophila testis niche. ..
  42. Zhang L, Jilg N, Shao R, Lin W, Fusco D, Zhao H, et al. IL28B inhibits hepatitis C virus replication through the JAK-STAT pathway. J Hepatol. 2011;55:289-98 pubmed publisher
    ..Our data demonstrate that IL28A, IL28B, and IL29 signal through the JAK-STAT pathway to inhibit HCV. These data suggest possible applications of new approaches in HCV treatment. ..
  43. Wu M, Pastor Pareja J, Xu T. Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature. 2010;463:545-8 pubmed publisher
    ..Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers. ..
  44. Davies E, Fuller M. Regulation of self-renewal and differentiation in adult stem cell lineages: lessons from the Drosophila male germ line. Cold Spring Harb Symp Quant Biol. 2008;73:137-45 pubmed publisher
  45. Gorissen M, de Vrieze E, Flik G, Huising M. STAT genes display differential evolutionary rates that correlate with their roles in the endocrine and immune system. J Endocrinol. 2011;209:175-84 pubmed publisher
  46. Minakhina S, Tan W, Steward R. JAK/STAT and the GATA factor Pannier control hemocyte maturation and differentiation in Drosophila. Dev Biol. 2011;352:308-16 pubmed publisher
    ..Stat and Pnr represent two essential factors controlling blood cell maturation in the developing lymph gland and exert their functions both in a cell-autonomous and non-cell-autonomous manner. ..
  47. Vidal O, Stec W, Bausek N, Smythe E, Zeidler M. Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. J Cell Sci. 2010;123:3457-66 pubmed publisher
    ..As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade. ..
  48. Cherry C, MATUNIS E. Epigenetic regulation of stem cell maintenance in the Drosophila testis via the nucleosome-remodeling factor NURF. Cell Stem Cell. 2010;6:557-67 pubmed publisher
    ..Thus, local signals cooperate with specific chromatin-remodeling complexes in intact niches to coordinately regulate a common set of target genes to prevent premature stem cell differentiation. ..
  49. Araki T, van Egmond W, Van Haastert P, Williams J. Dual regulation of a Dictyostelium STAT by cGMP and Ca2+ signalling. J Cell Sci. 2010;123:837-41 pubmed publisher
  50. Issigonis M, Tulina N, de Cuevas M, Brawley C, Sandler L, Matunis E. JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche. Science. 2009;326:153-6 pubmed publisher
    ..Thus, in niches housing multiple stem cell types, negative feedback loops can modulate signaling, preventing one stem cell population from outcompeting the other. ..
  51. Guo C, Zhang Y, Yang L, Yang X, Wu Y, Liu D, et al. The JAK and STAT family members of the mandarin fish Siniperca chuatsi: molecular cloning, tissues distribution and immunobiological activity. Fish Shellfish Immunol. 2009;27:349-59 pubmed publisher
    ..These results suggest that mandarin fish has the JAK/STAT signal transduction pathways similar to those in mammals, and these signalling pathways may play an important role in regulation of antiviral responses in fish. ..
  52. Himpe E, Kooijman R. Insulin-like growth factor-I receptor signal transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Biofactors. 2009;35:76-81 pubmed publisher
    ..Theoretically, dysregulation of CIS or SOCS may affect IGF-I-mediated effects on body growth, cell differentiation, proliferation, and cell survival. ..
  53. Pirault J, Polyzos K, Petri M, Ketelhuth D, Bäck M, Hansson G. The inflammatory cytokine interferon-gamma inhibits sortilin-1 expression in hepatocytes via the JAK/STAT pathway. Eur J Immunol. 2017;47:1918-1924 pubmed publisher
    ..This reduced the expression of sortilin-1, while disrupting the IFN-? signaling pathway prevented the effect. These data unravel an intricate mechanism by which inflammation modulates receptors involved in lipoprotein turnover. ..