TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

The NF-kappa B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-kappa B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-kappa B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF alpha-induced NF-kappa B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-kappa B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-kappa B signal and regulates cell growth. (C) 2012 Elsevier Inc. All rights reserved.