Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan.
Int J Mol Sci. 2019 May 30;20(11):2668. doi: 10.3390/ijms20112668.
Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.
丝裂原活化蛋白激酶（MAPKs）是信号转导和细胞反应的关键调节剂。MAPKs 的异常与多种疾病有关。双特异性磷酸酶（DUSPs）去磷酸化许多关键的信号分子，包括 MAPKs，从而调节 MAPK 活性的持续时间、幅度或时空特征。因此，DUSPs 需要得到适当的控制。蛋白质翻译后的修饰，如泛素化、磷酸化、甲基化和乙酰化，在蛋白质稳定性和活性的调节中起着重要作用。泛素化对于控制蛋白质降解、激活和相互作用至关重要。对于 DUSPs 来说，泛素化诱导了八种 DUSPs 的降解，即 DUSP1、DUSP4、DUSP5、DUSP6、DUSP7、DUSP8、DUSP9 和 DUSP16。此外，磷酸化增强了 DUSP2 和 DUSP10 的蛋白质稳定性。DUSP14 的甲基化诱导泛素化刺激其磷酸酶活性。在这篇综述中，我们总结了通过翻译后修饰调节 DUSP 稳定性和泛素化的知识。
