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

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Abstract

WTX encodes a tumor suppressor gene inactivated in Wilms tumor and recently implicated in WNT signaling through enhancement of cytoplasmic /j-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 WT1mediated 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.

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Rivera, M. N., Kim, W. J., Wells, J., Stone, A., Burger, A., Coffman, E. J., … Haber, D. A. (2009). The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity. Proceedings of the National Academy of Sciences of the United States of America, 106(20), 8338–8343. https://doi.org/10.1073/pnas.0811349106

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