CLIC4 and Schnurri-2: A dynamic duo in TGFβ signaling with broader implications in cellular homeostasis and disease

Abstract

CLIC4 is a highly conserved, multifunctional member of the chloride intracellular channel family of proteins. The protein is largely cytoplasmic but translocates to the nucleus upon a variety of stimuli including TGFβ, TNFα and etoposide. Nuclear resident CLIC4 causes growth arrest, terminal differentiation and apoptosis. Recently, it was discovered that TGFβ causes CLIC4 to associate with Schnurri-2 and together they translocate to the nucleus and dissociate thereafter. The nuclear function of CLIC4 was further illuminated by the discovery that CLIC4 enhances TGFβ signaling by associating with phospho-Smad2 and 3 and preventing their dephosphorylation. Enhanced TGFβ dependent gene expression and growth inhibition are downstream consequences of this activity of CLIC4. In this article, we speculate on other consequences of the CLIC4 relation to TGFβ signaling and the potential for CLIC4 to participate in other cellular functions related to normal homeostasis and disease. © 2010 Landes Bioscience.