Downregulation of active IKK beta by Ro52-mediated autophagy.
Downregulation of active IKK beta by Ro52-mediated autophagy.
复制标题
DOI：
10.1016/j.molimm.2010.05.004
复制
发表时间：
2010-08
影响因子：
3.6
通讯作者：
Kamitani T
中科院分区：
文献类型：
--
作者：
Niida M;Tanaka M;Kamitani T
核转录因子κB被激活后，移位到细胞核内，引发许多生物学事件。这种核因子-κB信号主要是由蛋白激酶IKKβ诱导的。在这个信号通路的早期，IKKβ被几个因素磷酸化以激活，例如促炎细胞因子和人类T细胞白血病病毒1型的Tax癌蛋白。在表达Tax蛋白的细胞中，IKKβ被持续磷酸化，从而长期激活NF-κB信号。但激活的IKKβ通过E3泛素连接酶Ro52与单核苷酸结合，并且IKKβ诱导的NF-κB信号下调。然而，下调的机制一直不为人知。在这里，我们证明了Ro52介导的单泛素化参与了活性IKKβ到自噬小体的亚细胞易位。此外，利用报告分析，我们发现Ro52抑制了IKKβ诱导的NF-κB信号，并且这种抑制被自噬抑制剂所阻断。这些结果表明，Ro52介导的单泛素化在通过自噬下调活性IKKβ的过程中起着关键作用。
Upon activation, NF-κB translocates into the nucleus and initiates many biological events. This NF-κB signaling is mainly induced by the protein kinase IKKβ. Early in this signaling pathway, IKKβ 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, IKKβ is persistently phosphorylated, which chronically activates NF-κB signaling. But the active IKKβ is conjugated with a monoubiquitin by the E3 ubiquitin ligase Ro52, and the IKKβ-induced NF-κB 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 IKKβ to autophagosomes. Furthermore, using reporter assays, we show that Ro52 suppresses IKKβ-induced NF-κB 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 IKKβ through autophagy.
登录
查看更多内容
影响因子：
4.8
作者：
Carter, RS;Pennington, KN;Ballard, DW
通讯作者：
Ballard, DW
影响因子：
3.3
作者：
Campbell, Edward M.;Dodding, Mark P.;Hope, Thomas J.
通讯作者：
Hope, Thomas J.
影响因子：
56.9
作者：
Delhase, M;Hayakawa, M;Karin, M
通讯作者：
Karin, M
影响因子：
4.8
作者：
Tanaka, H;Fujita, N;Tsuruo, T
通讯作者：
Tsuruo, T
影响因子：
4.8
作者：
Kamitani, T;Kito, K;Yeh, ETH
通讯作者：
Yeh, ETH