たいじのじんぞう
しきゅうたい。とにょうさいかんにWT1がつよくはつげんしている。
せいじょうにはつげんしているようにせいぎょしている。

WordNet

the 23rd letter of the Roman alphabet (同)w, double-u

PrepTutorEJDIC

Watt / West; Western
wolfram(=tungsten)の原子記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/25 16:36:28」(JST)

wiki en

[Wiki en表示]

Wilms tumor protein is a protein that in humans is encoded by the WT1 gene.^[1]^[2]^[3]^[4]

Function[edit]

This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms' tumor, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.^[5]

Structure[edit]

The WT1 gene product shows similarity to the zinc fingers of the mammalian growth regulated early growth response protein 1 (EGR1) and (EGR2) proteins.^[6]

Clinical significance[edit]

Wilm's tumour tumor suppressor gene1 (WT1) causes is an embryonic malignancy of the kidney, affecting around 1 in 10,000 infants. It occurs in both sporadic and hereditary forms. Inactivation of WT1 causes Wilm's tumour, and Denys-Drash syndrome (DDS), leading to nephropathy and genital abnormalities. The WT1 protein has been found to bind a host of cellular factors, e.g. p53, a known tumor suppressor.^[3]^[7]^[8]^[9]

The serine protease HtrA2 binds to WT1 and it cleaves WT1 at multiple sites following the treatment with cytotoxic drugs.^[10]^[11]

Using immunohistochemistry, WT1 protein can be demonstrated in the cell nuclei of 75% of mesotheliomas and in 93% of ovarian serous carcinomas, as well as in benign mesothelium and fallopian tube epithelium. This allows these tumours to be distinguished from other, similar, cancers, such as adenocarcinoma. Antibodies to the WT1 protein, however, also frequently cross-react with cytoplasmic proteins in a variety of benign and malignant cells, so that only nuclear staining can be considered diagnostic.^[12]

Interactions[edit]

WT1 has been shown to interact with U2AF2,^[13] PAWR,^[14] UBE2I^[15] and WTAP.^[16]

RNA editing[edit]

There is some evidence for RNA editing of human WT1 mRNA.As with alternative splicing of the gene RNA editing increases the number of isoforms of this protein.^[17]^[18]

Editing is tissue specific and developmentally regulated. Editing shown to be restricted in testis and kidney in the rat.^[17] Editing of this gene product has been found to occur in mice and rats as well as humans.^[17]^[19]

Editing type[edit]

The editing site is found at nucleotide position 839 found in exon 6 of the gene.It causes a codon change from a Proline codon (CCC) to a Leucine codon (CUC)^[17]

The type of editing is a Uridine to Cytidine( U to C) base change .The editing reaction is thought to be an amidation of uridine which converts it to a Cytidine.The relevance of this editing is unknown as is the enzyme responsible for this editing.The region where editing occurs like that of other editing sites e.g. ApoB mRNA editing is conserved.Mice, rat and humans have conserved sequences flanking the editing site consiting of 10 nucleotides before the editing site and four after the site.^[17]

Effects of editing[edit]

RNA editing results in an alternative amino acid being translated.^[17] The changes in amino acid occur in a region identified as a domain involved in transcription activation function.^[20]

Editing has been shown to decrease repressive regulation of transcription of growth promoting genes in vitro compared to the non edited protein. Although the physiological role of editing has yet to be determined, suggestions have been made that editing may play a role in the pathogenesis of Wilms tumour.^[19]

References[edit]

^ Burgin AB, Parodos K, Lane DJ, Pace NR (February 1990). "The excision of intervening sequences from Salmonella 23S ribosomal RNA". Cell 60 (3): 405–14. doi:10.1016/0092-8674(90)90592-3. PMID 2406020. Cite uses deprecated parameters (help)
^ Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH (February 1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell 60 (3): 509–20. doi:10.1016/0092-8674(90)90601-A. PMID 2154335. Cite uses deprecated parameters (help)
^ ^a ^b Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA (February 1990). "Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping". Nature 343 (6260): 774–8. doi:10.1038/343774a0. PMID 2154702. Cite uses deprecated parameters (help)
^ Huang A, Campbell CE, Bonetta L, McAndrews-Hill MS, Chilton-MacNeill S, Coppes MJ, Law DJ, Feinberg AP, Yeger H, Williams BR (November 1990). "Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor". Science 250 (4983): 991–4. doi:10.1126/science.2173145. PMID 2173145. Cite uses deprecated parameters (help)
^ "Entrez Gene: WT1 Wilms tumor 1".
^ Han Y, San-Marina S, Yang L, Khoury H, Minden MD (2007). "The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells.". Breast Cancer Res 9 (4): R43. doi:10.1186/bcr1743. PMC 2206716. PMID 17634147.
^ Rauscher FJ (July 1993). "The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor". FASEB J. 7 (10): 896–903. PMID 8393820. Cite uses deprecated parameters (help)
^ Buckler AJ, Pelletier J, Haber DA, Glaser T, Housman DE (March 1991). "Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development". Mol. Cell. Biol. 11 (3): 1707–12. PMC 369476. PMID 1671709. Cite uses deprecated parameters (help)
^ Little MH, Prosser J, Condie A, Smith PJ, Van Heyningen V, Hastie ND (June 1992). "Zinc finger point mutations within the WT1 gene in Wilms tumor patients". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4791–5. PMC 49173. PMID 1317572. Cite uses deprecated parameters (help)
^ Essafi A, Hastie ND (January 2010). "WT1 the oncogene: a tale of death and HtrA". Mol. Cell 37 (2): 153–5. doi:10.1016/j.molcel.2010.01.010. PMID 20122396. Cite uses deprecated parameters (help)
^ Hartkamp J, Carpenter B, Roberts SG (January 2010). "The Wilms' tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi". Mol. Cell 37 (2): 159–71. doi:10.1016/j.molcel.2009.12.023. PMC 2815029. PMID 20122399. Cite uses deprecated parameters (help)
^ Leong AS-Y, Cooper K, Leong FJW-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 447–448. ISBN 1-84110-100-1.
^ Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (October 1998). "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes". Genes Dev. 12 (20): 3217–25. doi:10.1101/gad.12.20.3217. PMC 317218. PMID 9784496. Cite uses deprecated parameters (help)
^ Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y (December 1996). "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1". Mol. Cell. Biol. 16 (12): 6945–56. PMC 231698. PMID 8943350. Cite uses deprecated parameters (help)
^ Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF (October 1996). "Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9". J. Biol. Chem. 271 (40): 24811–6. doi:10.1074/jbc.271.40.24811. PMID 8798754. Cite uses deprecated parameters (help)
^ Little NA, Hastie ND, Davies RC (September 2000). "Identification of WTAP, a novel Wilms' tumour 1-associating protein". Hum. Mol. Genet. 9 (15): 2231–9. doi:10.1093/oxfordjournals.hmg.a018914. PMID 11001926. Cite uses deprecated parameters (help)
^ ^a ^b ^c ^d ^e ^f Sharma PM, Bowman M, Madden SL, Rauscher FJ, Sukumar S (March 1994). "RNA editing in the Wilms' tumor susceptibility gene, WT1". Genes Dev. 8 (6): 720–31. PMID 7926762. Cite uses deprecated parameters (help)
^ Wagner KD, Wagner N, Schedl A (May 2003). "The complex life of WT1". J. Cell. Sci. 116 (Pt 9): 1653–8. doi:10.1242/jcs.00405. PMID 12665546. Cite uses deprecated parameters (help)
^ ^a ^b Mrowka C, Schedl A (November 2000). "Wilms' tumor suppressor gene WT1: from structure to renal pathophysiologic features". J. Am. Soc. Nephrol. 11 Suppl 16: S106–15. PMID 11065340. Cite uses deprecated parameters (help)
^ Wang ZY, Qiu QQ, Deuel TF (May 1993). "The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains". J. Biol. Chem. 268 (13): 9172–5. PMID 8486616. Cite uses deprecated parameters (help)

External links[edit]

GeneReviews/NCBI/NIH/UW entry on Aniridia
OMIM entries on Aniridia
GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview
http://darned.ucc.ie

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 小児におけるステロイド抵抗性特発性ネフローゼ症候群 steroid resistant idiopathic nephrotic syndrome in children
2. 急性骨髄性白血病の分子遺伝学 molecular genetics of acute myeloid leukemia
3. 急性骨髄性白血病の予後 prognosis of acute myeloid leukemia
4. 微細欠失症候群（1番～11番染色体） microdeletion syndromes chromosomes 1 to 11
5. ウィルムス腫瘍の症状、診断、および病期分類 presentation diagnosis and staging of wilms tumor

English Journal

Giant benign lymphangioendothelioma.

Revelles JM, Díaz JL, Angulo J, Santonja C, Kutzner H, Requena L.SourceDepartment of Dermatology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Journal of cutaneous pathology.J Cutan Pathol.2012 Oct;39(10):950-6. doi: 10.1111/j.1600-0560.2012.01971.x. Epub 2012 Jul 27.
Benign lymphangioendothelioma is a rare locally infiltrative vascular neoplasm, presenting as a slow-growing, asymptomatic, reddish-violaceous plaque. Histopathologically, it is characterized by irregular and thin-walled vascular spaces, lined by a single and discontinuous layer of flat endothelial
PMID 22834950
PMID 22958045

Japanese Journal

胆道がんに期待される新規薬剤について (特集肝・胆・膵腫瘍の薬物療法 : 最近の進歩)

上野誠
腫瘍内科 9(6), 684-687, 2012-06
NAID 40019380065

腫瘍マーカー (造血器腫瘍学 : 基礎と臨床の最新研究動向) -- (造血器腫瘍の診断と治療)

柴山浩彦
日本臨床 70 (1018 増刊2), 176-180, 2012-04
NAID 40019281372

Related Pictures

★リンクテーブル★

リンク元	「ウィルムス腫瘍」「癌抑制遺伝子」「11番染色体」
拡張検索	「WT1 gene」
関連記事	「W」「WT」

「ウィルムス腫瘍」

Wilms tumor 1
	; PDB rendering based on 1xf7.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1XF7, 2JP9, 2JPA, 2PRT, 3HPJ, 3MYJ
Identifiers
Symbols	WT1; AWT1; EWS-WT1; GUD; NPHS4; WAGR; WIT-2; WT33
External IDs	OMIM: 607102 MGI: 98968 HomoloGene: 11536 GeneCards: WT1 Gene
Gene Ontology
Molecular function	• RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; • sequence-specific DNA binding transcription factor activity; • RNA binding; • protein binding; • zinc ion binding; • sequence-specific DNA binding; • transcription regulatory region DNA binding; • C2H2 zinc finger domain binding;
Cellular component	• nucleus; • nucleoplasm; • nucleolus; • cytoplasm; • nuclear speck;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • vasculogenesis; • ureteric bud development; • branching involved in ureteric bud morphogenesis; • kidney development; • regulation of organ formation; • regulation of transcription, DNA-dependent; • regulation of transcription from RNA polymerase II promoter; • induction of apoptosis; • germ cell development; • thorax and anterior abdomen determination; • heart development; • sex determination; • negative regulation of cell proliferation; • RNA splicing; • gonad development; • male gonad development; • tissue development; • negative regulation of translation; • negative regulation of cell growth; • adrenal gland development; • male genitalia development; • epithelial cell differentiation; • glomerulus development; • glomerular basement membrane development; • adrenal cortex formation; • camera-type eye development; • negative regulation of apoptotic process; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • mesenchymal to epithelial transition; • positive regulation of heart growth; • diaphragm development; • cardiac muscle cell fate commitment; • visceral serous pericardium development; • cellular response to cAMP; • cellular response to gonadotropin stimulus; • metanephric mesenchyme development; • glomerular visceral epithelial cell differentiation; • posterior mesonephric tubule development; • metanephric epithelium development; • metanephric S-shaped body morphogenesis; • negative regulation of metanephric glomerular mesangial cell proliferation; • positive regulation of male gonad development; • negative regulation of female gonad development; • positive regulation of metanephric ureteric bud development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;