title: CLIC4 and Schnurri-2: a dynamic duo in TGF-beta 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 TGF-beta, TNF-alpha and etoposide. Nuclear resident CLIC4 causes growth arrest, terminal differentiation and apoptosis. Recently, it was discovered that TGF-beta 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 TGF-beta signaling by associating with phospho-Smad2 and 3 and preventing their dephosphorylation. Enhanced TGF-beta 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 TGF-beta signaling and the potential for CLIC4 to participate in other cellular functions related to normal homeostasis and disease.
authors.affiliation: Laboratory of Cancer Biology and Genetics, 37 Convent Drive, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Shukla
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Yuspa
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004194:Disease; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D004268:DNA-Binding Proteins; D016212:Transforming Growth Factor beta