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

被引：56

作者：

Rivera, Miguel N. ^{[1
]}

Kim, Woo Jae ^{[1
]}

Wells, Julie ^{[1
]}

Stone, Amanda ^{[1
]}

Burger, Alexa ^{[1
]}

Coffman, Erik J. ^{[1
]}

Zhang, Jianmin ^{[1
]}

Haber, Daniel A. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 20期

基金：

美国国家卫生研究院;

关键词：

cancer biology; subcellular localization; tumor suppression; WILMS-TUMOR; BETA-CATENIN; GENE; RELAXATION; ACTIVATION; MUTATIONS; PROTEIN; KIDNEY;

D O I：

10.1073/pnas.0811349106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：8338 / 8343

页数：6

共 27 条

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