| Popis: |
FOXL2 is a transcription factor critical for ovarian function. It has been implicated in diverse cellular processes, including apoptosis, the control of cell cycle or the regulation of steroid hormone synthesis. Our recent studies show that FOXL2 is involved in a large number of regulatory actions essential for the maintenance of granulosa cell fate. We have also identified hundreds of direct and indirect targets of estrogen receptor beta, of which one third are also targets of FOXL2. Accumulating evidence shows that both factors modulate, through a coherent feed-forward loop, a number of common targets. Many of the FOXL2/ERbeta targets are involved in cell migration, invasion and adhesion. Beyond the study of its transcriptional targets, the identification of the various interactors of FOXL2 is crucial to understand its diverse cellular roles. To reliably identify partners of endogenous FOXL2, we performed a proteome-wide analysis using co-immunoprecipitation in the murine granulosa cell-derived AT29c and the pituitary-derived alpha-T3 cell lines. Following a stringent selection, we identified a core set of about 250 (direct and indirect) partners common to both cell lines. Their analysis showed that FOXL2 belongs to complexes involved in mRNA processing, chromatin remodeling and DNA replication and repair. We further validated interactions with selected partners, suggesting an unexpected role for FOXL2. Our analysis expands the number of direct and indirect transcriptional targets and partners of both FOXL2, which deserve investigation in the context of adult-type granulosa cell tumors whose molecular diagnostic hallmark is the presence of the C134 W FOXL2 pathogenic variant. |
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