Downregulation of active IKKβ by Ro52-mediated autophagy

Upon activation NF-kappa B translocates into the nucleus and inmates many biological events This NF-kappa B signaling is mainly induced by the protein kinase IKK beta Early in this signaling pathway IKK beta is phosphorylated for activation by several factors such as pro-inflammatory cytokines and the Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) In cells expressing Tax protein IKK beta is persistently phosphorylated which chronically activates NF-kappa B signaling But the active IKK beta is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52 and the IKK beta-induced NF-kappa B signaling is downregulated However the mechanism of the downregulation has been unknown Here we show that Ro52-mediated monoubiquitination is involved in the subcellular translocation of active IKK beta to autophagosomes Furthermore using reporter assays we show that Ro52 suppresses IKK beta-induced NF-kappa B signaling and that this suppression is blocked by an autophagy inhibitor These results suggest that Ro52-mediated monoubiquitination plays a critical role in the downregulation of active IKK beta through autophagy (C) 2010 Elsevier Ltd All rights reserved