A four-and-a-half LIM protein FHL2 acts as a coactivator for the Wilms' tumor suppressor WT1 during gonadal differentiation
An essential step during sex determination is the maintenance of the Müllerian duct in females which gives rise to oviduct, uterus and the upper part of vagina and its regression in males caused by the expression of Müllerian inhibiting substance (MIS). The Wilms' tumor suppressor (WT1) and the orphan nuclear receptor steroidogenic factor 1 (SF-1) bind cooperatively to the promoter of MIS and activate its transcription. In the ovary, on the other hand, the orphan nuclear receptor DAX-1 binds to SF-1. The binding inhibits WT1/SF-1 transactivation and thereby suppresses induction of MIS gene expression. In addition, WT1 itself is also responsible for directly upregulating DAX-1 transcription. In summary, little is known about the molecular mechanisms that regulates transcription of the MIS gene. Importantly, so far no bona fide coactivators for WT1 have been described.
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