<br>Ssu72 双特异性蛋白磷酸酶：从基因到疾病,International Journal of Molecular Sciences

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Ssu72 双特异性蛋白磷酸酶：从基因到疾病
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2021-04-06 , DOI: 10.3390/ijms22073791
Soeun Hwang ₁ , Min-Hee Kim ₁ , Chang-Woo Lee _{1,

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Affiliation

超过 70% 的真核蛋白质受磷酸化调节。然而，去磷酸化对抗磷酸化的机制研究较少。根据底物特异性特征和催化结构域的序列同源性，磷酸酶被分为 104 个不同的组。其中，使磷酸丝氨酸/苏氨酸和磷酸酪氨酸去磷酸化的双特异性磷酸酶（DUSP）对于细胞稳态非常重要。 Ssu72是一种新研究的具有双重特异性的磷酸酶，可以使磷酸丝氨酸/苏氨酸和磷酸酪氨酸去磷酸化。它对于细胞生长信号、新陈代谢和免疫激活很重要。 Ssu72 最初被鉴定为 RNA 聚合酶 II C 端结构域 Ser5 和 Ser7 残基的磷酸酶。与其他磷酸酶不同，它更喜欢其底物内丝氨酸-脯氨酸基序的顺式构型并调节 Pin1。最近有报道称，Ssu72可以调节细胞周期中姐妹染色单体的凝聚和重复染色体的分离。此外，Ssu72 似乎参与 T 细胞受体信号传导、端粒调节，甚至响应各种应激和损伤信号的肝细胞稳态的调节。在这篇综述中，我们旨在总结 Ssu72 磷酸酶的各种功能、它们对疾病的影响以及潜在的治疗适应症。

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Ssu72 Dual-Specific Protein Phosphatase: From Gene to Diseases

More than 70% of eukaryotic proteins are regulated by phosphorylation. However, the mechanism of dephosphorylation that counteracts phosphorylation is less studied. Phosphatases are classified into 104 distinct groups based on substrate-specific features and the sequence homologies in their catalytic domains. Among them, dual-specificity phosphatases (DUSPs) that dephosphorylate both phosphoserine/threonine and phosphotyrosine are important for cellular homeostasis. Ssu72 is a newly studied phosphatase with dual specificity that can dephosphorylate both phosphoserine/threonine and phosphotyrosine. It is important for cell-growth signaling, metabolism, and immune activation. Ssu72 was initially identified as a phosphatase for the Ser5 and Ser7 residues of the C-terminal domain of RNA polymerase II. It prefers the cis configuration of the serine–proline motif within its substrate and regulates Pin1, different from other phosphatases. It has recently been reported that Ssu72 can regulate sister chromatid cohesion and the separation of duplicated chromosomes during the cell cycle. Furthermore, Ssu72 appears to be involved in the regulation of T cell receptor signaling, telomere regulation, and even hepatocyte homeostasis in response to a variety of stress and damage signals. In this review, we aim to summarize various functions of the Ssu72 phosphatase, their implications in diseases, and potential therapeutic indications.

更新日期：2021-04-06

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