Wilms' tumor protein; WT1 protein (WT1, WT3)
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Function
- role in cell survival & proliferation (putative)
- role in transcriptional regulation (putative)
- recognizes & binds to the DNA sequence 5'-CGCCCCCGC-3'
- interacts with WTIP (putative)
- interacts with ZNF224 via the Zn+2-finger region
- interacts with WTAP & SRY
- one isoform binds the amphiregulin promoter & activates transcription[3]
- downstream regulated genes may also include those for nephrin, podocalyxin[4] & cyclin E[5]
- WT1 functions in gonad formation & sex determination.
- targets include sry, wnt4, dax1 & MIS.
Structure
- belongs to the EGR C2H2-type Zn+2-finger protein family
- contains 4 C2H2-type Zn+2 fingers
Compartment
Alternative splicing
- named isoforms=5
- alternative splicing may give rise to transcription factors with different DNA-binding specificities.
- exons 5 & 9 are alternatively spliced
- exon 5 is mammal specific & contains a domain which permits association with prostate apoptosis factor 4 (par4). Exon 9 codes for a KTS sequence between the 3rd & 4th zinc finger.
- forms containing the KTS sequence are denoted WT[+KTS], those without WT[-KTS]; the ratio of the two is nearly constant in all cell types[4]
Expression
- expressed in kidney & a subset of hematopoietic cells
- embryonic development:
- urogenital system
- spleen
- portions of brain & spinal cord
- may play role in neuronal development
- mesothelial organs
- diaphragm
- proliferating coelomic epithelium
- epicardium & subepicardial mesenchyme
- adult expression:
- kidney
- Sertoli cells in testes
- granulosa cells in ovaries
Pathology
- defects in WT1 are the cause of
- chromosomal translocation t(11;22)(p13;q12) involving WT1 with EWSR1 is associated with desmoplastic small round cell tumor (DSRCT)
expression associated with hypoxia/ischemia
- normally absent in adult heart
- re-expressed in smooth muscle & endothelial cells or coronary arteries after myocardial infarction or myocardial ischemia
- colocalizes with cell proliferation markers & VEGF
- neoplasms (positive immunostaining)[5]
- Wilms tumor/nephroblastoma
- mesothelioma
- AML
- desmoplastic small round cell tumor of lung
- metanephric adenoma
- ovarian epithelial neoplasms
- rhabdoid tumor
More general terms
References
- ↑ Rauscher FJ et al Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science 250:1259 1990 PMID: https://www.ncbi.nlm.nih.gov/pubmed/2244209
- ↑ Bickmore WA et al Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science 257:235 1992 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1321494
- ↑ 3.0 3.1 Lee et al, The Wilms tumor suppressor WT1 encodes a transcriptional activator amphregulin. Cell 98:663-673, 1999 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10490105
- ↑ 4.0 4.1 4.2 Wagner KD et al, The complex life of WT1 J Cell Science 116:1653-8, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12565546
- ↑ 5.0 5.1 5.2 Loeb DM et al. Cyclin E is a target of WT1 transcriptional repression J Biol Chem 277(22):19627-32, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11919196
- ↑ Richard DJ, Schumacher V, Royer-Pokora B, Roberts SG. Genes & Development 15:328-39, 2001 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/11159913 Free PMC Article
- ↑ <Internet> http://pathologyoutlines.com/stains.html 18 May 2003
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7490
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/WT1ID78.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=WT1
- ↑ UniProt http://www.uniprot.org/uniprot/P19544.html
Database
- UniProt: http://www.uniprot.org/uniprot/P19544.html
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7490
- OMIM: https://mirror.omim.org/entry/136680
- OMIM: https://mirror.omim.org/entry/137357
- OMIM: https://mirror.omim.org/entry/194070
- OMIM: https://mirror.omim.org/entry/194080
- OMIM: https://mirror.omim.org/entry/256370
- OMIM: https://mirror.omim.org/entry/607102
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7490