TC1 (C8orf4) is upregulated by cellular stress and mediates heat shock response

Abstract

TC1 (C8orf4) is associated with aggressive behavior and poor survival in cancer. We have recently reported that it is a target gene of NF-kappaB and regulates the Wnt/beta-catenin pathway. Here, we show that TC1 is upregulated by various cellular stresses and mediates heat shock response. Heat shock and other cellular stresses including H2O2, 12-O-tetradecanoylphorbol 13-acetate (TPA), lipopolysaccharide (LPS), and UV enhance TC1 transcription in HeLa, KATO-III, HEK293T, and HK cells. TC1 protein then moves into the nuclei independently of NF-kappaB activation. TC1 upregulates heat shock proteins, and TC1-knockdown inhibits stress-induced downstream regulation significantly. Heat shock factor 1(HSF1) and TC1 upregulate each other, suggesting a potential positive feedback in the heat shock response regulation. Our data suggest that TC1 is a novel heat shock response regulator.