TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin–proteasome system

TRIM11 is a member of the tripartite-motif-containing protein family and is known to destabilize humanin, an inhibitor of Alzheimer-like neuronal insults. In this study, we demonstrate that TRIM11 interacts with activator-recruited cofactor 105-kDa component (ARC105) that mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor β (TGFβ) signaling. Co-expression of TRIM11 increased ARC105 degradation but a proteasome inhibitor suppressed this. Co-expression of TRIM11 and ARC105 also increased ubiquitination of ARC105. In addition, TRIM11 suppressed ARC105-mediated transcriptional activation induced with TGFβ in a reporter assay. These results suggest that TRIM11, with the ubiquitin–proteasome pathway, regulates ARC105 function in TGFβ signaling.