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The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity.

Rivera M.N., Kim W.J., Wells J., Stone A., Burger A., Coffman E.J., Zhang J., Haber D.A.

WTX encodes a tumor suppressor gene inactivated in Wilms tumor and recently implicated in WNT signaling through enhancement of cytoplasmic beta-catenin (CTNNB1) degradation. Here, we report that WTX translocates to the nucleus, a property that is modified by an endogenous splicing variant and is modulated by a nuclear export inhibitor. WTX is present in distinct subnuclear structures and co-localizes with the paraspeckle marker p54NRB/NONO, suggesting a role in transcriptional regulation. Notably, WTX binds WT1, another Wilms tumor suppressor and stem cell marker that encodes a zinc-finger transcription factor, and enhances WT1-mediated transcription of Amphiregulin, an endogenous target gene. Together, these observations suggest a role for WTX in nuclear pathways implicated in the transcriptional regulation of cellular differentiation programs.

Proc. Natl. Acad. Sci. U.S.A. 106:8338-8343(2009) [PubMed] [Europe PMC]

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