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dc.contributor.authorRae, Fiona Kaven
dc.contributor.authorMartinez, Gemma
dc.contributor.authorGillinder, Kevin Robert
dc.contributor.authorSmith, Aaron
dc.contributor.authorShooter, Gary
dc.contributor.authorForrest, Alistair Raymond
dc.contributor.authorGrimmond, Sean Michael
dc.contributor.authorLittle, Melissa Helen
dc.description.abstractThe Wilms' tumour suppressor gene, WT1, encodes a zinc-finger protein that is mutated in Wilms' tumours and other malignancies. WT1 is one of the earliest genes expressed during kidney development. WT1 proteins can activate and repress putative target genes in vitro, although the in vivo relevance of such target genes often remains unverified. To better understand the role of WT1 in tumorigenesis and kidney development, we need to identify downstream target genes. In this study, we have expression profiled human embryonic kidney 293 cells stably transfected to allow inducible WT1 expression and mouse mesonephric M15 cells transfected with a WT1 antisense construct to abolish endogenous expression of all WT1 isoforms to identify WT1-responsive genes. The complementary overlap between the two cell lines revealed a pronounced repression of genes involved in cholesterol biosynthesis by WT1. This pathway is transcriptionally regulated by the sterol responsive element-binding proteins (SREBPs). Here, we provide evidence that the C-terminal end of the WT1 protein can directly interact with SREBP, suggesting that WT1 may modify the transcriptional function of SREBPs via a direct protein-protein interaction. Therefore, the tumour suppressor activities of WT1 may be achieved by repressing the mevalonate pathway, thereby controlling cellular proliferation and promoting terminal differentiation.
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchOncology and carcinogenesis
dc.titleAnlaysis of complementary expression profiles following WT1 induction versus repression reveals the cholesterol/fatty acid synthetic pathways as a possible major target of WT1
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.description.notepublicTitle has a misspelling of "Analysis" because that is how this article was published and subsequently cited in major citation tools.
gro.rights.copyright© 2004 Nature Publishing Group. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextNo Full Text
gro.griffith.authorForrest, Alistair RR.

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