Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1
Deactivation of the kinase IKK by CUEDC2 through recruitment of the phosphatase PP1
复制标题
DOI：
10.1038/ni.1600
复制
发表时间：
2008-05-01
影响因子：
30.5
通讯作者：
Zhang, Xue-Min
中科院分区：
文献类型：
--
作者：
Li, Hui-Yan;Liu, Hui;Zhang, Xue-Min
尽管在阐明IKK激酶激活的分子机制方面取得了快速进展，但调节IKK失活的过程仍然未知。在这里，我们证明了含有CUE结构域的2（CUEDC 2）与IKK α和IKK β相互作用，并通过降低IKK的磷酸化和活化来抑制转录因子NF-κ B B的活化。值得注意的是，CUEDC 2还与蛋白磷酸酶1（PP 1）的调节亚基GADD 34相互作用。我们发现IKK、CUEDC 2和PP 1存在于一个复合物中，并且IKK响应于炎症刺激如肿瘤坏死因子而从该复合物中释放。CUEDC 2通过将PP 1招募到复合体来使IKK失活。因此，CUEDC 2作为一种衔接蛋白，通过募集PP 1靶向IKK进行去磷酸化和失活。
Despite rapid progress in elucidating the molecular mechanisms of activation of the kinase IKK, the processes that regulate IKK deactivation are still unknown. Here we demonstrate that CUE domain-containing 2 (CUEDC2) interacted with IKK alpha and IKK beta and repressed activation of the transcription factor NF-kappa B by decreasing phosphorylation and activation of IKK. Notably, CUEDC2 also interacted with GADD34, a regulatory subunit of protein phosphatase 1 (PP1). We found that IKK, CUEDC2 and PP1 existed in a complex and that IKK was released from the complex in response to inflammatory stimuli such as tumor necrosis factor. CUEDC2 deactivated IKK by recruiting PP1 to the complex. Therefore, CUEDC2 acts as an adaptor protein to target IKK for dephosphorylation and inactivation by recruiting PP1.