Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation
Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation
复制标题
DOI：
10.1016/j.febslet.2006.07.032
复制
发表时间：
2006-08
期刊：
影响因子：
3.5
通讯作者：
Tomoharu Takeuchi;Takayasu Kobayashi;S. Tamura;H. Yokosawa
中科院分区：
文献类型：
--
作者：
Tomoharu Takeuchi;Takayasu Kobayashi;S. Tamura;H. Yokosawa
ISG15是一种干扰素上调的泛素样蛋白，与多种细胞蛋白共价结合（ISGylation）。在这项研究中，我们发现蛋白磷酸酶2C β（PP2C β），其功能在核因子κ B（NF-κ B）途径中通过TGF-β激活的激酶的去磷酸化，被ISG化，通过NF-κ B荧光素酶报告基因分析显示，PP2C β活性被ISG 15，UBE 1L和UbcH 8的共表达抑制。我们确定了PP2C β的ISGylation位点，并构建了其ISGylation抗性突变体。与野生型相比，该突变体抑制NF-κ B途径，即使在ISG 15、UBE 1L和UbcH 8存在下也是如此。因此，我们提出ISG化负调控PP2C β活性。
ISG15, an interferon-upregulated ubiquitin-like protein, is covalently conjugated to various cellular proteins (ISGylation). In this study, we found that protein phosphatase 2Cβ (PP2Cβ), which functions in the nuclear factor κB (NF-κB) pathway via dephosphorylation of TGF-β-activated kinase, was ISGylated, and analysis by NF-κB luciferase reporter assay revealed that PP2Cβ activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. We determined the ISGylation sites of PP2Cβ and constructed its ISGylation-resistant mutant. In contrast to the wild type, this mutant suppressed the NF-κB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, we propose that ISGylation negatively regulates PP2Cβ activity.