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抑癌蛋白磷酸酶 5 共伴侣的结构与功能。

Structure and function of the co-chaperone protein phosphatase 5 in cancer.

机构信息

Department of Urology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.

Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.

出版信息

Cell Stress Chaperones. 2020 May;25(3):383-394. doi: 10.1007/s12192-020-01091-3. Epub 2020 Apr 2.

DOI:10.1007/s12192-020-01091-3
PMID:32239474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7193036/
Abstract

Protein phosphatase 5 (PP5) is a serine/threonine protein phosphatase that regulates many cellular functions including steroid hormone signaling, stress response, proliferation, apoptosis, and DNA repair. PP5 is also a co-chaperone of the heat shock protein 90 molecular chaperone machinery that assists in regulation of cellular signaling pathways essential for cell survival and growth. PP5 plays a significant role in survival and propagation of multiple cancers, which makes it a promising target for cancer therapy. Though there are several naturally occurring PP5 inhibitors, none is specific for PP5. Here, we review the roles of PP5 in cancer progression and survival and discuss the unique features of the PP5 structure that differentiate it from other phosphoprotein phosphatase (PPP) family members and make it an attractive therapeutic target.

摘要

蛋白磷酸酶 5(PP5)是一种丝氨酸/苏氨酸蛋白磷酸酶,可调节多种细胞功能,包括甾体激素信号转导、应激反应、增殖、凋亡和 DNA 修复。PP5 也是热休克蛋白 90 分子伴侣机制的共伴侣,有助于调节细胞信号通路,这些通路对细胞存活和生长至关重要。PP5 在多种癌症的存活和增殖中起着重要作用,这使其成为癌症治疗的有希望的靶点。尽管有几种天然存在的 PP5 抑制剂,但没有一种是针对 PP5 的。在这里,我们综述了 PP5 在癌症进展和存活中的作用,并讨论了 PP5 结构的独特特征,使其与其他磷酸蛋白磷酸酶(PPP)家族成员区分开来,并使其成为有吸引力的治疗靶点。

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本文引用的文献

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PLoS One. 2019 Aug 19;14(8):e0221289. doi: 10.1371/journal.pone.0221289. eCollection 2019.
2
Exploring the role of active site Mn ions in the binding of protein phosphatase 5 with its substrate using molecular dynamics simulations.利用分子动力学模拟探究活性位点 Mn 离子在蛋白磷酸酶 5 与其底物结合中的作用。
Biochem Biophys Res Commun. 2019 Apr 9;511(3):612-618. doi: 10.1016/j.bbrc.2019.02.113. Epub 2019 Feb 28.
3
Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.FNIP1 的翻译后调控为分子伴侣 HSP90 创造了一个变阻器。
Cell Rep. 2019 Jan 29;26(5):1344-1356.e5. doi: 10.1016/j.celrep.2019.01.018.
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The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.抗肿瘤药物 LB-100 是蛋白磷酸酶 2A(PPP2CA)和 5(PPP5C)的催化抑制剂,与 PPP5C 的活性位点催化金属配位。
Mol Cancer Ther. 2019 Mar;18(3):556-566. doi: 10.1158/1535-7163.MCT-17-1143. Epub 2019 Jan 24.
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Protein phosphatase 5 and the tumor suppressor p53 down-regulate each other's activities in mice.蛋白磷酸酶 5 和肿瘤抑制因子 p53 在小鼠中相互下调对方的活性。
J Biol Chem. 2018 Nov 23;293(47):18218-18229. doi: 10.1074/jbc.RA118.004256. Epub 2018 Sep 27.
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Palbociclib enhances radiosensitivity of hepatocellular carcinoma and cholangiocarcinoma via inhibiting ataxia telangiectasia-mutated kinase-mediated DNA damage response.帕博西尼通过抑制共济失调毛细血管扩张突变激酶介导的 DNA 损伤反应增强肝癌和胆管癌的放射敏感性。
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Serine/threonine protein phosphatase 5 is a potential therapeutic target in cholangiocarcinoma.丝氨酸/苏氨酸蛋白磷酸酶 5 是胆管癌的一个潜在治疗靶点。
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