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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-2-28
pubmed:abstractText
The Wilms' tumor gene Wt1 encodes a zinc finger protein, which is required for normal formation of the genitourinary system and mesothelial tissues. Our recent findings indicate that Wt1 also plays a critical role in the development of ganglion cells in the vertebrate retina. Here we show that the POU-domain factor Pou4f2 (formerly Brn-3b), which is necessary for retinal ganglion cell survival, is up-regulated in human embryonic kidney (HEK)293 cells with stable Wt1 expression. Consistent with our previous observations of increased Pou4f2 mRNA in stably Wt1-transfeced HEK293 cells [EMBO J. 21 (2002) 1398], endogenous Pou4f2 was also elevated at the protein level in the HEK293 transfectants as well as in U2OS osteosarcoma cells that expressed an inducible Wt1 isoform. Transient co-transfection of a Wt1 expression construct activated a Pou4f2 promoter-reporter construct approximately 4-fold. Stimulation of the Pou4f2 promoter required a Wt1 binding element that was similar to a degenerative consensus site previously identified in other Wt1 responsive genes. Double-immunofluorescent labeling revealed co-expression of Pou4f2 and Wt1 in glomerular podocytes of adult kidney and in developing retinal ganglion cells of mouse embryos. Pou4f2 immunoreactivity was absent from the retinas of Wt1(-/-) embryos. In conclusion, we identified Pou4f2 as a novel downstream target gene of Wt1. Co-localization of both proteins in glomerular podocytes of the kidney and in developing retinal ganglion cells suggests a role for Wt1-Pou4f2 interaction in these tissues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
305
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-23
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12609742-Animals, pubmed-meshheading:12609742-Cell Line, pubmed-meshheading:12609742-DNA-Binding Proteins, pubmed-meshheading:12609742-Electrophoretic Mobility Shift Assay, pubmed-meshheading:12609742-Female, pubmed-meshheading:12609742-Humans, pubmed-meshheading:12609742-Immunoblotting, pubmed-meshheading:12609742-Immunohistochemistry, pubmed-meshheading:12609742-Kidney, pubmed-meshheading:12609742-Luciferases, pubmed-meshheading:12609742-Male, pubmed-meshheading:12609742-Mice, pubmed-meshheading:12609742-Mice, Inbred C57BL, pubmed-meshheading:12609742-Protein Binding, pubmed-meshheading:12609742-Recombinant Fusion Proteins, pubmed-meshheading:12609742-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:12609742-Retina, pubmed-meshheading:12609742-Transcription Factor Brn-3, pubmed-meshheading:12609742-Transcription Factor Brn-3B, pubmed-meshheading:12609742-Transcription Factors, pubmed-meshheading:12609742-Transcriptional Activation, pubmed-meshheading:12609742-Transfection, pubmed-meshheading:12609742-Tumor Cells, Cultured, pubmed-meshheading:12609742-WT1 Proteins
pubmed:year
2003
pubmed:articleTitle
The Wilms' tumor suppressor Wt1 encodes a transcriptional activator of the class IV POU-domain factor Pou4f2 (Brn-3b).
pubmed:affiliation
Johannes-Müller-Institut für Physiologie, Humboldt-Universität, Charité, Tucholskystrasse 2, 10117 Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't