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. (c) 2010 Elsevier Ltd. All rights reserved.
Upon activation, NF-kappaB translocates into the nucleus and initiates many biological events. Tpan class="Chemical">hisNF-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. (c) 2010 Elsevier Ltd. All rights reserved.
Authors: F Mercurio; H Zhu; B W Murray; A Shevchenko; B L Bennett; J Li; D B Young; M Barbosa; M Mann; A Manning; A Rao Journal: Science Date: 1997-10-31 Impact factor: 47.728
Authors: J Tsukada; M Misago; Y Serino; R Ogawa; S Murakami; M Nakanishi; S Tonai; Y Kominato; I Morimoto; P E Auron; S Eto Journal: Blood Date: 1997-10-15 Impact factor: 22.113
Authors: Michael A Mandell; Ashish Jain; John Arko-Mensah; Santosh Chauhan; Tomonori Kimura; Christina Dinkins; Guido Silvestri; Jan Münch; Frank Kirchhoff; Anne Simonsen; Yongjie Wei; Beth Levine; Terje Johansen; Vojo Deretic Journal: Dev Cell Date: 2014-08-07 Impact factor: 12.270
Authors: Martina Di Rienzo; Alessandra Romagnoli; Manuela Antonioli; Mauro Piacentini; Gian Maria Fimia Journal: Cell Death Differ Date: 2020-01-22 Impact factor: 15.828