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The Wilms Tumor Suppressor Protein (WT1) splice variants WT1(‐KTS) and WT1(+KTS) show distinct influences on different control levels of the Renin gene expression
Author(s) -
Steege Andreas,
Fähling Michael,
Martinka Peter,
Patzak Andreas,
Brinkmeier Thomas,
Persson Pontus B.,
Scholz Holger,
Mrowka Ralf
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.969.16
Subject(s) - wilms' tumor , biology , gene , messenger rna , renin–angiotensin system , splice , alternative splicing , suppressor , cancer research , microbiology and biotechnology , endocrinology , genetics , blood pressure
Clinical studies indicate that Renin gene expression is controlled by the WT1 splice variants WT1(‐KTS) and WT1(+KTS). We investigated the underlying mechanisms through which they influence the Renin gene expression. Over expression of both WT1 variants in human kidney cells decrease the Renin protein level. Reporter gene studies demonstrate that the WT1 splice variants modulate the Renin promoter activity either directly (+KTS form) or through interactions within a regulatory region [hRENc] (both variants). WT1(+KTS) has an activating influence mediated by the Renin promoter. The WT1(+KTS) variant is able to interact with the Renin mRNA‐UTRs in contrast to the WT1(‐KTS) form. We show that the Renin mRNA undergoes a translocation into a translational inactive compartment after over expression of the WT1(+KTS) variant. The posttranscriptional influence of WT1(+KTS) may be responsible for a translational arrest of Renin synthesis, which explain the decrease of the Renin protein following WT1(+KTS) over expression. Both variants of the Wilms Tumor Suppressor Protein inhibit the Renin synthesis through distinct and different mechanisms and thus may participate in a hyperreninism in patients suffering from Wilms Tumor. Research support: Pontus B. Persson, Institut für Vegetative Physiologie, Charité‐Universitäts medizin Berlin, Tucholskystr. 2, 10117 Berlin, Germany