Mechanisms of transcriptional regulation by WT1 (Wilms' tumour 1).

The WT1 (Wilms' tumour 1) gene encodes a zinc finger transcription factor and RNA-binding protein that direct the development of several organs and tissues. WT1 manifests both tumour suppressor and oncogenic activities, but the reasons behind these opposing functions are still not clear. As a transcriptional regulator, WT1 can either activate or repress numerous target genes resulting in disparate biological effects such as growth, differentiation and apoptosis. The complex nature of WT1 is exemplified by a plethora of isoforms, post-translational modifications and multiple binding partners. How WT1 achieves specificity to regulate a large number of target genes involved in diverse physiological processes is the focus of the present review. We discuss the wealth of the growing molecular information that defines our current understanding of the versatility and utility of WT1 as a master regulator of organ development, a tumour suppressor and an oncogene.

[1]  M. Radomski,et al.  The Transcription Factor Wilms Tumor 1 Regulates Matrix Metalloproteinase-9 through a Nitric Oxide-Mediated Pathway , 2007, The Journal of Immunology.

[2]  D. Bonthron,et al.  Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  A. Caricasole,et al.  Wilms' tumour-suppressor protein isoforms have opposite effects on Igf2 expression in primary embryonic cells, independently of p53 genotype. , 1998, British Journal of Cancer.

[4]  A. Schedl,et al.  YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. , 1999, Development.

[5]  N. Hastie,et al.  Actin: a novel interaction partner of WT1 influencing its cell dynamic properties , 2010, Oncogene.

[6]  D. Wilhelm,et al.  The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1. , 2002, Genes & development.

[7]  J. Licht,et al.  WT1-mediated Transcriptional Activation Is Inhibited by Dominant Negative Mutant Proteins (*) , 1995, The Journal of Biological Chemistry.

[8]  Z. Wang,et al.  A second transcriptionally active DNA-binding site for the Wilms tumor gene product, WT1. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  K. Wagner,et al.  Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms' tumor suppressor Wt1. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[10]  A. Gronenborn,et al.  Molecular determinants of mammmalian sex. , 1996, Trends in biochemical sciences.

[11]  E. Toska,et al.  Classification of a frameshift/extended and a stop mutation in WT1 as gain-of-function mutations that activate cell cycle genes and promote Wilms tumour cell proliferation , 2014, Human molecular genetics.

[12]  D. Haber,et al.  Induction of p21 by the Wilms' tumor suppressor gene WT1. , 1997, Cancer research.

[13]  M. Mosevitsky Nerve ending "signal" proteins GAP-43, MARCKS, and BASP1. , 2005, International review of cytology.

[14]  H. Werner,et al.  Inhibition of cellular proliferation by the Wilms' tumor suppressor WT1 is associated with suppression of insulin-like growth factor I receptor gene expression , 1995, Molecular and cellular biology.

[15]  D. Haber,et al.  A Functional Interaction with CBP Contributes to Transcriptional Activation by the Wilms Tumor Suppressor WT1* , 2001, The Journal of Biological Chemistry.

[16]  J. Kreidberg WT1 and kidney progenitor cells , 2010, Organogenesis.

[17]  E. Fraenkel,et al.  Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development , 2010, Development.

[18]  D. Housman,et al.  Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in expression during follicle development and repression of inhibin-alpha gene promoter. , 1995, Molecular endocrinology.

[19]  Youhua Liu,et al.  PINCH1 Is Transcriptional Regulator in Podocytes That Interacts with WT1 and Represses Podocalyxin Expression , 2011, PloS one.

[20]  N. Tommerup,et al.  Ciao 1 Is a Novel WD40 Protein That Interacts with the Tumor Suppressor Protein WT1* , 1998, The Journal of Biological Chemistry.

[21]  Stefan G. E. Roberts,et al.  Prohibitin is required for transcriptional repression by the WT1-BASP1 complex , 2013, Oncogene.

[22]  B. Kerem,et al.  Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations. , 2000, Human molecular genetics.

[23]  Rong Zheng,et al.  Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex* , 2011, The Journal of Biological Chemistry.

[24]  D. Wilhelm,et al.  The LIM-only coactivator FHL2 modulates WT1 transcriptional activity during gonadal differentiation. , 2002, Biochimica et biophysica acta.

[25]  K. Samuel,et al.  Acute Multiple Organ Failure in Adult Mice Deleted for the Developmental Regulator Wt1 , 2011, PLoS genetics.

[26]  Sandip K. Mishra,et al.  Par-4 Transcriptionally Regulates Bcl-2 through a WT1-binding Site on the bcl-2 Promoter* , 2003, Journal of Biological Chemistry.

[27]  K. Wagner,et al.  A splice variant of the Wilms' tumour suppressor Wt1 is required for normal development of the olfactory system , 2005, Development.

[28]  A. Feinberg,et al.  The genetics of BWS associated tumors , 1999 .

[29]  H. Taylor,et al.  WT1 represses HOX gene expression in the regulation of gynaecologic tumour histologic type , 2008, Journal of cellular and molecular medicine.

[30]  N. Hastie,et al.  Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. , 2003, Human molecular genetics.

[31]  Anwar Hossain,et al.  The Human Sex-determining Gene SRY Is a Direct Target of WT1 * , 2001, The Journal of Biological Chemistry.

[32]  L. Ercolani,et al.  LLC-PK1 Cell Growth Is Repressed by WT1 Inhibition of G-protein αi−2 Protooncogene Transcription (*) , 1995, The Journal of Biological Chemistry.

[33]  G I Bell,et al.  Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. , 1992, Science.

[34]  K. Wagner,et al.  Transcriptional regulation by the Wilms' tumour suppressor protein WT1. , 2004, Biochemical Society transactions.

[35]  Adrian V. Lee,et al.  The WT1 Wilms' tumor suppressor gene product interacts with estrogen receptor-alpha and regulates IGF-I receptor gene transcription in breast cancer cells. , 2005, Journal of molecular endocrinology.

[36]  D. Cook,et al.  A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. , 1993, Oncogene.

[37]  D. Richard,et al.  Par4 is a coactivator for a splice isoform-specific transcriptional activation domain in WT1. , 2001, Genes & development.

[38]  G. Montano,et al.  Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms. , 2010, Human molecular genetics.

[39]  L. Fattore,et al.  Role of WT1-ZNF224 interaction in the expression of apoptosis-regulating genes. , 2013, Human molecular genetics.

[40]  S. Roberts Transcriptional regulation by WT1 in development. , 2005, Current opinion in genetics & development.

[41]  N. Hastie,et al.  Expression in Xenopus oocytes shows that WT1 binds transcripts in vivo, with a central role for zinc finger one , 2003, Journal of Cell Science.

[42]  K. Coombes,et al.  Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative transcriptional targets using cDNA microarray expression profiling of genetically defined Wilms' tumors , 2003, Oncogene.

[43]  K. Lao,et al.  World of Reproductive Biology , 2012 .

[44]  Z. Wang,et al.  Products of alternatively spliced transcripts of the Wilms' tumor suppressor gene, wt1, have altered DNA binding specificity and regulate transcription in different ways. , 1995, Oncogene.

[45]  R. Miller,et al.  WT1-interacting protein and ZO-1 translocate into podocyte nuclei after puromycin aminonucleoside treatment. , 2005, American journal of physiology. Renal physiology.

[46]  J. H. Park,et al.  Control of epigenetic states by WT1 via regulation of de novo DNA methyltransferase 3A. , 2013, Human molecular genetics.

[47]  S. Grimmond,et al.  Anlaysis of complementary expression profiles following WT1 induction versus repression reveals the cholesterol/fatty acid synthetic pathways as a possible major target of WT1 , 2004, Oncogene.

[48]  N D Hastie,et al.  RNA binding by the Wilms tumor suppressor zinc finger proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[49]  A. Jochemsen,et al.  Physical Interaction between Wilms Tumor 1 and p73 Proteins Modulates Their Functions* , 2000, The Journal of Biological Chemistry.

[50]  Xin-Yuan Fu,et al.  Wilms' tumor 1 and signal transducers and activators of transcription 3 synergistically promote cell proliferation: a possible mechanism in sporadic Wilms' tumor. , 2006, Cancer research.

[51]  Fei Gao,et al.  Wt1 ablation and Igf2 upregulation in mice result in Wilms tumors with elevated ERK1/2 phosphorylation. , 2011, The Journal of clinical investigation.

[52]  Angeliki Kotsianti,et al.  WT1 regulates the expression of the major glomerular podocyte membrane protein Podocalyxin , 2001, Current Biology.

[53]  A. Schedl,et al.  WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis. , 2002, Human molecular genetics.

[54]  J. Schelling,et al.  A WT1 Co-regulator Controls Podocyte Phenotype by Shuttling between Adhesion Structures and Nucleus* , 2004, Journal of Biological Chemistry.

[55]  Abdelkader Essafi,et al.  Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin , 2009, Nature Genetics.

[56]  A. Gronenborn,et al.  Molecular determinants ofmammalian sex , 1996 .

[57]  P. Hohenstein,et al.  WT1 in disease: shifting the epithelial–mesenchymal balance , 2012, The Journal of pathology.

[58]  S. Nakamura,et al.  Inhibitory effect of calmodulin on phosphorylation of NAP-22 with protein kinase C. , 1994, The Journal of biological chemistry.

[59]  Xu-wen Liu,et al.  The Wilms' Tumor Gene Product WT1 Mediates the Down-regulation of the Rat Epidermal Growth Factor Receptor by Nerve Growth Factor in PC12 Cells* , 2001, The Journal of Biological Chemistry.

[60]  The Wilms’ tumor gene (WT1) regulates E-cadherin expression and migration of prostate cancer cells , 2013, Molecular Cancer.

[61]  J. Licht,et al.  The Receptor Tyrosine Kinase Regulator Sprouty1 Is a Target of the Tumor Suppressor WT1 and Important for Kidney Development* , 2003, Journal of Biological Chemistry.

[62]  J. Testa,et al.  Molecular Cloning of the cDNA and Chromosome Localization of the Gene for Human Ubiquitin-conjugating Enzyme 9* , 1996, The Journal of Biological Chemistry.

[63]  B. Tycko,et al.  A pathologic link between Wilms tumor suppressor gene, WT1, and IFI16. , 2008, Neoplasia.

[64]  D. Haber,et al.  E1B 55K sequesters WT1 along with p53 within a cytoplasmic body in adenovirus-transformed kidney cells , 1998, Oncogene.

[65]  M. Ballmaier,et al.  The Wilms' tumor suppressor Wt1 activates transcription of the erythropoietin receptor in hematopoietic progenitor cells , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[66]  Y. Kaneda,et al.  The Transcription Factors Tbx18 and Wt1 Control the Epicardial Epithelial-Mesenchymal Transition through Bi-Directional Regulation of Slug in Murine Primary Epicardial Cells , 2013, PloS one.

[67]  M. Taglienti,et al.  Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa , 2005, Development.

[68]  C. Roberts,et al.  Regulation of Insulin-Like Growth Factor I Receptor Promoter Activity by Wild-Type and Mutant Versions of the WT1 Tumor Suppressor1. , 1999, Endocrinology.

[69]  A. Brookes,et al.  Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression. , 2001, Biochemical and biophysical research communications.

[70]  A. Jochemsen,et al.  Wilms' tumor 1-KTS isoforms induce p53-independent apoptosis that can be partially rescued by expression of the epidermal growth factor receptor or the insulin receptor. , 1997, Cancer research.

[71]  J. Pelletier,et al.  Inhibition of Wilms Tumor 1 Transactivation by Bone Marrow Zinc Finger 2, a Novel Transcriptional Repressor* , 2002, The Journal of Biological Chemistry.

[72]  H. Scholz,et al.  Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development* , 2013, The Journal of Biological Chemistry.

[73]  A. Poustka,et al.  Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping , 1990, Nature.

[74]  S. Sukumar,et al.  Differential effects of Wilms tumor WT1 splice variants on the insulin receptor promoter. , 1997, Biochemical and molecular medicine.

[75]  T. Hunter,et al.  Inhibition of the DNA-binding and transcriptional repression activity of the Wilms' tumor gene product, WT1, by cAMP-dependent protein kinase-mediated phosphorylation of Ser-365 and Ser-393 in the zinc finger domain , 1997, Oncogene.

[76]  M. Sporn,et al.  Repression of the transforming growth factor-beta 1 gene by the Wilms' tumor suppressor WT1 gene product. , 1994, Molecular endocrinology.

[77]  M. Rivera,et al.  The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity , 2009, Proceedings of the National Academy of Sciences.

[78]  P. Romaniuk,et al.  Characterization of RNA aptamer binding by the Wilms' tumor suppressor protein WT1. , 2001, Biochemistry.

[79]  Anwar Hossain,et al.  Role of Wilms Tumor 1 (WT1) in the Transcriptional Regulation of the Mullerian-Inhibiting Substance Promoter1 , 2003, Biology of reproduction.

[80]  A. Gannon,et al.  The Wilms’ tumour suppressor protein WT1 acts as a key transcriptional repressor of the human thromboxane A2 receptor gene in megakaryocytes , 2008, Journal of cellular and molecular medicine.

[81]  D. Haber,et al.  The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis. , 1995, Genes & Development.

[82]  S. Sukumar,et al.  Cyclin E Is a Target of WT1 Transcriptional Repression* , 2002, The Journal of Biological Chemistry.

[83]  P. Houghton,et al.  Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) Are Regulators of STIM1 Expression* , 2010, The Journal of Biological Chemistry.

[84]  G. Hammer,et al.  Wilms' Tumor 1 and Dax-1 Modulate the Orphan Nuclear Receptor SF-1 in Sex-Specific Gene Expression , 1998, Cell.

[85]  V. Huff,et al.  Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene , 2011, Nature Reviews Cancer.

[86]  Holger Scholz,et al.  Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1. , 2005, Genes & development.

[87]  J. Pelletier,et al.  Insights into the physiological role of WT1 from studies of genetically modified mice. , 2004, Physiological genomics.

[88]  Z. Wang,et al.  The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene. , 1992, The Journal of biological chemistry.

[89]  E. Toska,et al.  Repression of transcription by WT1-BASP1 requires the myristoylation of BASP1 and the PIP2-dependent recruitment of histone deacetylase. , 2012, Cell reports.

[90]  F. Pociot,et al.  Strain Dependent Rat iNOS Promoter Activity—Correlation to Identified WT1 Transcription Factor Binding Site , 2003, Autoimmunity.

[91]  H. Pass,et al.  Wilms' tumor suppressor gene expression in rat and human mesothelioma. , 1994, Cancer research.

[92]  M. Eccles,et al.  A novel insertional mutation at the third zinc finger coding region of the WT1 gene in Denys-Drash syndrome. , 1993, Human molecular genetics.

[93]  C. McCoy,et al.  The Wilms' tumor suppressor, WT1, inhibits 12-O-tetradecanoylphorbol-13-acetate activation of the multidrug resistance-1 promoter. , 1999, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[94]  M. Minden,et al.  Transcriptional activation of c-myc proto-oncogene by WT1 protein , 2004, Oncogene.

[95]  V. Sukhatme,et al.  Transcriptional repression of the insulin-like growth factor I receptor (IGF-I-R) gene by the tumor suppressor WT1 involves binding to sequences both upstream and downstream of the IGF-I-R gene transcription start site. , 1994, The Journal of biological chemistry.

[96]  Matthias Mann,et al.  BASP1 Is a Transcriptional Cosuppressor for the Wilms' Tumor Suppressor Protein WT1 , 2004, Molecular and Cellular Biology.

[97]  J. Martinez-Barbera,et al.  Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage , 2007, Development.

[98]  K. Wagner,et al.  The Wilms' tumor gene Wt1 is required for normal development of the retina , 2002, The EMBO journal.

[99]  M. Bernfield,et al.  Transcriptional activation of the syndecan-1 promoter by the Wilms' tumor protein WT1. , 1996, Oncogene.

[100]  P. Bornstein,et al.  The Wilms' tumor gene product represses the transcription of thrombospondin 1 in response to overexpression of c-Jun , 1999, Oncogene.

[101]  S. Tejpar,et al.  Upregulation of Wilms' tumor gene 1 (WT1) in desmoid tumors , 2005, International journal of cancer.

[102]  S. Hewitt,et al.  Differential Function of Wilms Tumor Gene WT1 Splice Isoforms in Transcriptional Regulation (*) , 1996, The Journal of Biological Chemistry.

[103]  C. B. Patel,et al.  Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. , 2001, Cancer research.

[104]  J. Licht,et al.  WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. , 2005, Cancer research.

[105]  J. Morris,et al.  Repression of Pax-2 by WT1 during normal kidney development. , 1995, Development.

[106]  N. Hastie,et al.  hnRNP-U directly interacts with WT1 and modulates WT1 transcriptional activation , 2007, Oncogene.

[107]  N. Hayashi,et al.  Identification of the Calmodulin-binding Domain of Neuron-specific Protein Kinase C Substrate Protein CAP-22/NAP-22 , 1999, The Journal of Biological Chemistry.

[108]  Yijiang Chen,et al.  WT1 Promotes Invasion of NSCLC via Suppression of CDH1 , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[109]  M. von Knebel Doeberitz,et al.  WT1 is a tumor‐associated antigen in colon cancer that can be recognized by in vitro stimulated cytotoxic T cells , 2004, International journal of cancer.

[110]  P. Stanhope-Baker,et al.  The Wilms Tumor Suppressor-1 Target Gene Podocalyxin Is Transcriptionally Repressed by p53* , 2004, Journal of Biological Chemistry.

[111]  D. Housman,et al.  Expression of the Wilms' tumor gene WT1 in the murine urogenital system. , 1991, Genes & development.

[112]  Holger Scholz,et al.  A role for the Wilms' tumor protein WT1 in organ development. , 2005, Physiology.

[113]  G. Fraizer,et al.  Regulation of vascular endothelial growth factor, VEGF, gene promoter by the tumor suppressor, WT1. , 2007, Frontiers in bioscience : a journal and virtual library.

[114]  K. Wagner,et al.  The major podocyte protein nephrin is transcriptionally activated by the Wilms' tumor suppressor WT1. , 2004, Journal of the American Society of Nephrology : JASN.

[115]  F. Rauscher,et al.  Regulation of ornithine decarboxylase gene expression by the Wilms' tumor suppressor WT1. , 1996, Nucleic acids research.

[116]  E. Reddy,et al.  Cellular Factors Binding to a Novel cis-Acting Element Mediate Steroid Hormone Responsiveness of Mouse Mammary Tumor Virus Promoter (*) , 1995, The Journal of Biological Chemistry.

[117]  K. Wagner,et al.  The Wilms Tumor Suppressor Wt1 Promotes Cell Adhesion through Transcriptional Activation of the α4integrin Gene* , 2006, Journal of Biological Chemistry.

[118]  Allen R. Chen,et al.  The antiapoptotic gene A1/BFL1 is a WT1 target gene that mediates granulocytic differentiation and resistance to chemotherapy. , 2006, Blood.

[119]  K. Wagner,et al.  The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo , 2008, Oncogene.

[120]  D. Housman,et al.  Alternative splicing and genomic structure of the Wilms tumor gene WT1. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[121]  J. Pelletier,et al.  Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter. , 2001, Physiological genomics.

[122]  L. Boxer,et al.  Repression of the c-myb Gene by WT1 Protein in T and B Cell Lines (*) , 1995, The Journal of Biological Chemistry.

[123]  D. Haber,et al.  SUMO-1 Modification of the Wilms’ Tumor Suppressor WT1 , 2004, Cancer Research.

[124]  T. Akiyama,et al.  Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1). , 1996, Oncogene.

[125]  B. Carpenter,et al.  Regulation of the Wilms' tumour suppressor protein transcriptional activation domain , 1999, Oncogene.

[126]  K. Semba,et al.  Physical and functional interaction between the HCMV IE2 protein and the Wilms' tumor suppressor WT1. , 2000, Biochemical and biophysical research communications.

[127]  David Housman,et al.  WT-1 is required for early kidney development , 1993, Cell.

[128]  I. Weissman,et al.  The Wilms’ tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis , 2007, Leukemia.

[129]  Z. Wang,et al.  The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains. , 1993, The Journal of biological chemistry.

[130]  M. Rivera,et al.  A Novel Wilms Tumor 1 (WT1) Target Gene Negatively Regulates the WNT Signaling Pathway* , 2010, The Journal of Biological Chemistry.

[131]  J. Hartkamp,et al.  HtrA2, taming the oncogenic activities of WT1 , 2010, Cell cycle.

[132]  W. Hsu,et al.  The Wilms' tumor suppressor Wt1 regulates Coronin 1B expression in the epicardium. , 2013, Experimental cell research.

[133]  X. Xia,et al.  Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. , 1993, The Journal of biological chemistry.

[134]  F. Gao,et al.  Expression of Inhibin-Alpha Is Regulated Synergistically by Wilms' Tumor Gene 1 (Wt1) and Steroidogenic Factor-1 (Sf1) in Sertoli Cells , 2013, PloS one.

[135]  M. Wilkinson,et al.  Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis. , 2006, Genes & development.

[136]  K. Wagner,et al.  Oxygen‐regulated expression of the Wilms’ tumor suppressor Wt1 involves hypoxia‐inducible factor‐1 (HIF‐1) , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[137]  M. Ladomery,et al.  Multiple roles for the Wilms' tumor suppressor, WT1. , 1999, Cancer research.

[138]  C. Englert,et al.  The Wilms' tumor suppressor WT1 enhances CD95L expression and promotes activation‐induced cell death in leukemic T cells , 2014, International journal of cancer.

[139]  D. Housman,et al.  An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor , 1990, Cell.

[140]  U. Kim,et al.  In vivo and in vitro analyses of Myc for differential promoter activities of the human telomerase (hTERT) gene in normal and tumor cells. , 1999, Biochemical and biophysical research communications.

[141]  J. Licht,et al.  Two N-terminal self-association domains are required for the dominant negative transcriptional activity of WT1 Denys-Drash mutant proteins. , 1997, Biochemical and biophysical research communications.

[142]  C. Englert,et al.  Wilms' Tumor Protein Wt1 Is an Activator of the Anti-Müllerian Hormone Receptor Gene Amhr2 , 2007, Molecular and Cellular Biology.

[143]  N. Hastie,et al.  Life, Sex, and WT1 Isoforms— Three Amino Acids Can Make All the Difference , 2001, Cell.

[144]  J. Inoue,et al.  Transcriptional activity of testis-determining factor SRY is modulated by the Wilms’ tumor 1 gene product, WT1 , 2003, Oncogene.

[145]  T. Akiyama,et al.  WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. , 1994, Blood.

[146]  B. Perbal,et al.  Regulation of nov by WT1: a potential role for nov in nephrogenesis. , 1996, Oncogene.

[147]  D. Harrison,et al.  Genetic interactions between the Wilms' tumor 1 gene and the p53 gene. , 2002, Cancer research.

[148]  N. Hastie,et al.  A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. , 2010, Human molecular genetics.

[149]  A. Lamond,et al.  WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes. , 1998, Genes & development.

[150]  J. Licht,et al.  A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1 , 1996, Molecular and cellular biology.

[151]  J. Hartkamp,et al.  The Wilms' Tumor Suppressor Protein WT1 Is Processed by the Serine Protease HtrA2/Omi , 2010, Molecular cell.

[152]  T. Kyo,et al.  Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[153]  J. Licht,et al.  E-cadherin Is a WT1 Target Gene* , 2000, The Journal of Biological Chemistry.

[154]  A. Gurney,et al.  Regulation of WT1 by phosphorylation: inhibition of DNA binding, alteration of transcriptional activity and cellular translocation. , 1996, The EMBO journal.

[155]  J. Licht,et al.  WT1 Induction of Mitogen-Activated Protein Kinase Phosphatase 3 Represents a Novel Mechanism of Growth Suppression , 2008, Molecular Cancer Research.

[156]  A. Schedl,et al.  Two Splice Variants of the Wilms' Tumor 1 Gene Have Distinct Functions during Sex Determination and Nephron Formation , 2001, Cell.

[157]  W. Hofmann,et al.  Characterization of the transcriptional regulatory region of the human WT1 gene. , 1993, Oncogene.

[158]  K. Malik,et al.  Autoregulation of the human WT1 gene promoter , 1994, FEBS letters.

[159]  J. Hartkamp,et al.  The role of the Wilms' tumour-suppressor protein WT1 in apoptosis. , 2008, Biochemical Society transactions.

[160]  Peter Hohenstein,et al.  The many facets of the Wilms' tumour gene, WT1. , 2006, Human molecular genetics.

[161]  J. Shay,et al.  Transcription of deleted mitochondrial DNA in human colon adenocarcinoma cells. , 1992, Human molecular genetics.

[162]  A. Chávez-Reyes,et al.  HER2/neu increases the expression of Wilms' Tumor 1 (WT1) protein to stimulate S-phase proliferation and inhibit apoptosis in breast cancer cells , 2005, Oncogene.

[163]  M. Little,et al.  Wnt-4 regulation by the Wilms' tumour suppressor gene, WT1 , 2002, Oncogene.

[164]  Xiaobin Han,et al.  Regulation of taurine transporter gene (TauT) by WT1 , 2003, FEBS letters.

[165]  M. Cam,et al.  Identification of Novel Wilms' Tumor Suppressor Gene Target Genes Implicated in Kidney Development* , 2007, Journal of Biological Chemistry.

[166]  Zhaoyi Wang,et al.  Induction of Rb-associated Protein (RbAp46) by Wilms’ Tumor Suppressor WT1 Mediates Growth Inhibition* , 1998, The Journal of Biological Chemistry.

[167]  A. C. Williams,et al.  Genomic imprinting at the WT1 gene involves a novel coding transcript (AWT1) that shows deregulation in Wilms' tumours. , 2003, Human molecular genetics.

[168]  S. Madden,et al.  Transcriptional repression mediated by the WT1 Wilms tumor gene product. , 1991, Science.

[169]  N. Little,et al.  Identification of WTAP, a novel Wilms' tumour 1-associating protein. , 2000, Human molecular genetics.

[170]  J. Davies,et al.  A wt1-controlled chromatin switching mechanism underpins tissue-specific wnt4 activation and repression. , 2011, Developmental cell.

[171]  G. Saunders,et al.  Expression of the Wilms' tumor gene (WT1) in human leukemias. , 1992, Leukemia.

[172]  V. V. Zakharov,et al.  The BASP1 family of myristoylated proteins abundant in axonal termini. Primary structure analysis and physico-chemical properties. , 1997, Biochimie.

[173]  Stefan G. E. Roberts,et al.  WT1 and its transcriptional cofactor BASP1 redirect the differentiation pathway of an established blood cell line , 2011, The Biochemical journal.

[174]  W. Gerald,et al.  The Wilms Tumor Suppressor WT1 Encodes a Transcriptional Activator of amphiregulin , 1999, Cell.

[175]  M. Gessler,et al.  The genomic organization and expression of the WT1 gene. , 1992, Genomics.

[176]  K. Miyagawa,et al.  Repression of promoters for the mouse insulin-like growth factor II-encoding gene (Igf-2) by products of the Wilms' tumour suppressor gene wt1. , 1995, Gene.

[177]  D. Housman,et al.  Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus , 1990, Cell.

[178]  K. Miyagawa,et al.  Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing , 1995, Cell.

[179]  Wang Wei,et al.  Di-n-ブチルフタレートは,マウス卵巣胞状濾胞における細胞周期およびアポトーシス経路に関与する遺伝子の発現を混乱させる , 2013 .

[180]  Stefan G. E. Roberts,et al.  Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiation , 2008, Nucleic acids research.

[181]  J. Pelletier,et al.  WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2 , 2003, Oncogene.

[182]  N. Hastie,et al.  The role of Wt1 in regulating mesenchyme in cancer, development, and tissue homeostasis. , 2012, Trends in genetics : TIG.

[183]  J. Pelletier,et al.  Repression of the retinoic acid receptor-alpha gene by the Wilms' tumor suppressor gene product, wt1. , 1995, Oncogene.

[184]  D. Haber,et al.  WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. , 1995, The EMBO journal.

[185]  Toshiki Yoshimine,et al.  Overexpression of the Wilms' tumor gene WT1 in primary astrocytic tumors , 2004, Cancer science.

[186]  C. Englert,et al.  The Wilms tumor suppressor gene wt1 is required for development of the spleen , 1999, Current Biology.

[187]  M. Ladomery,et al.  The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron. , 2006, Genes & development.

[188]  J. Licht,et al.  WT1 activates a glomerular-specific enhancer identified from the human nephrin gene. , 2004, Journal of the American Society of Nephrology : JASN.

[189]  D. Haber,et al.  WT1 induces expression of insulin-like growth factor 2 in Wilms' tumor cells. , 1995, Cancer research.

[190]  C. Y. Wang,et al.  WT1 modulates apoptosis by transcriptionally upregulating the bcl‐2 proto‐oncogene , 1999, The EMBO journal.

[191]  M. Ladomery,et al.  WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. , 2011, Cancer cell.

[192]  S. Madden,et al.  The Wilms' tumor suppressor gene WT1 is negatively autoregulated. , 1994, The Journal of biological chemistry.

[193]  Amy Bernard,et al.  Physical and functional interaction between WT1 and p53 proteins. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[194]  Jared M Flatow,et al.  An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1 , 2009, Proceedings of the National Academy of Sciences.

[195]  R. Ezzell,et al.  Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70. , 1998, Genes & development.

[196]  M. Minden,et al.  Wilms' Tumor 1 Suppressor Gene Mediates Antiestrogen Resistance via Down-Regulation of Estrogen Receptor-α Expression in Breast Cancer Cells , 2008, Molecular Cancer Research.

[197]  A. Jochemsen,et al.  WT1 proteins: functions in growth and differentiation. , 2001, Gene.

[198]  M. Ladomery,et al.  The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain. , 2006, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[199]  H. Werner,et al.  WT1-p53 Interactions in Insulin-like Growth Factor-I Receptor Gene Regulation* , 2003, The Journal of Biological Chemistry.

[200]  K. Wagner,et al.  The Wilms' tumor suppressor Wt1 encodes a transcriptional activator of the class IV POU-domain factor Pou4f2 (Brn-3b). , 2003, Gene.

[201]  J. Bard,et al.  The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo , 1993, Mechanisms of Development.

[202]  D. Loeb,et al.  WT1 Protein Directly Regulates Expression of Vascular Endothelial Growth Factor and Is a Mediator of Tumor Response to Hypoxia* , 2011, The Journal of Biological Chemistry.

[203]  J. Pelletier,et al.  The Wilms’ Tumor Suppressor Gene (wt1) Product Regulates Dax-1 Gene Expression during Gonadal Differentiation , 1999, Molecular and Cellular Biology.

[204]  B. Morris,et al.  WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo. , 2006, Experimental cell research.

[205]  E. Toska,et al.  WT1 regulates the development of the posterior taste field , 2014, Development.

[206]  H. Scholz,et al.  Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene. , 2006, Blood.

[207]  V. Sukhatme,et al.  Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. , 1993, Proceedings of the National Academy of Sciences of the United States of America.