Referenced in: none

Automatically associated channels: ClIC4 , Slo1

Title: TGF-beta signalling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3.

Authors: Anjali Shukla, Mariam Malik, Christophe Cataisson, Yan Ho, Travis Friesen, Kwang S Suh, Stuart H Yuspa

Journal, date & volume: Nat. Cell Biol., 2009 Jun , 11, 777-84

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19448624

Abstract
CLIC4 (chloride intracellular channel 4), a multifunctional protein that traffics between the cytoplasm and nucleus, interacts with Schnurri-2, a transcription factor in the bone morphogenetic protein (BMP) signalling pathway. Here we show that transforming growth factor beta (TGF-beta) promotes the expression of CLIC4 and Schnurri-2 as well as their association in the cytoplasm and their translocation to the nucleus. In the absence of CLIC4 or Schnurri-2, TGF-beta signalling is abrogated. Direct nuclear targeting of CLIC4 enhances TGF-beta signalling and removes the requirement for Schnurri-2. Nuclear CLIC4 associates with phospho (p)-Smad2 and p-Smad3, protecting them from dephosphorylation by nuclear phosphatases. An intact TGF-beta signalling pathway is essential for CLIC4-mediated growth-arrest. These results newly identify Schnurri-2 and CLIC4 as modifiers of TGF-beta signalling through their stabilization of p-Smad2 and 3 in the nucleus.