The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity.
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.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 20129, USA.
Miguel N
MN
Rivera
Woo Jae
WJ
Kim
Julie
J
Wells
Amanda
A
Stone
Alexa
A
Burger
Erik J
EJ
Coffman
Jianmin
J
Zhang
Daniel A
DA
Haber
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D066258:Amphiregulin; D002460:Cell Line; D066255:EGF Family of Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D025721:WT1 Proteins / Q000032:analysis / Q000378:metabolism*
C517118:AMER1 protein, human; C587848:AREG protein, human; D048868:Adaptor Proteins, Signal Transducing; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D025721:WT1 Proteins