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.
CITATION STYLE
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
Mendeley helps you to discover research relevant for your work.