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Mol Immunol. 2010 Aug;47(14):2378-87. doi: 10.1016/j.molimm.2010.05.004. Epub 2010 Jun 2.

Downregulation of active IKK beta by Ro52-mediated autophagy.

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Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.


Upon activation, NF-kappaB translocates into the nucleus and initiates many biological events. This NF-kappaB 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-kappaB signaling. But the active IKK beta is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52, and the IKK beta-induced NF-kappaB 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-kappaB 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.

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