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

  • Proc Natl Acad Sci U S A. 2009 May 19;106(20):8338-43. doi: 10.1073/pnas.0811349106.
Miguel N Rivera  1 ,  Woo Jae Kim ,  Julie Wells ,  Amanda Stone ,  Alexa Burger ,  Erik J Coffman ,  Jianmin Zhang ,  Daniel A Haber
Affiliations
  • 1. Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 20129, USA.
PMID: 19416806 DOI: 10.1073/pnas.0811349106
Abstract

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.