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The protein histidine phosphatase LHPP is a tumour suppressor

机译：组氨酸磷酸酶LHPP蛋白是一种肿瘤抑制因子

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摘要

Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins(1,2). Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.
机译：组氨酸磷酸化，即所谓的隐藏的磷酸化蛋白质组，是蛋白质翻译后修饰的特征不佳（1,2）。在这里，我们描述了组氨酸磷酸化在肿瘤发生中的作用。从mTOR驱动的肝细胞癌小鼠模型中对12种肿瘤的蛋白质组学分析表明，唯一已知的哺乳动物组氨酸激酶NME1和NME2被上调。相反，假定的组氨酸磷酸酶LHPP的表达在肿瘤中特异性下调。我们证明LHPP确实是蛋白质组氨酸磷酸酶。与这些观察结果一致，肝肿瘤中的整体组氨酸磷酸化明显上调。 LHPP在肝细胞癌小鼠模型中的持续肝表达降低了肿瘤负担并防止了肝功能的丧失。最后，在肝细胞癌患者中，LHPP的低表达与肿瘤严重程度增加和总生存期降低有关。因此，LHPP是一种蛋白质组氨酸磷酸酶和肿瘤抑制因子，表明组氨酸磷酸化失调是致癌的。

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  • 来源
    《Nature》 |2018年第7698期|678-682|共5页
  • 作者

    Hindupur Sravanth K.; Colombi Marco; Fuhs Stephen R.; Matter Matthias S.; Guri Yakir; Adam Kevin; Cornu Marion; Piscuoglio Salvatore; Ng Charlotte K. Y.; Betz Charles; Liko Dritan; Quagliata Luca; Moes Suzette; Jenoe Paul; Terracciano Luigi M.; Heim Markus H.; Hunter Tony; Hall Michael N.;

  • 作者单位

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

    Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland;

    Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

    Univ Hosp Basel, Inst Pathol, CH-4031 Basel, Switzerland;

    Univ Hosp Basel, Dept Biomed, CH-4031 Basel, Switzerland;

    Salk Inst Biol Studies, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;

    Univ Basel, Biozentrum, CH-4056 Basel, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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