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首页> 外文期刊>EMBO reports >Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1
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Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1

机译：Gli1诱导的脱硫蛋白酶USP48通过稳定GLI1助长胶质母细胞瘤肿瘤内血

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摘要

Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis. Importantly, USP48's effect on cell proliferation and tumorigenesis depends to some extent on Gli1. In addition, we find that the Sonic Hedgehog (SHH) pathway induces USP48 expression through Gli1-mediated transcriptional activation, which forms thus a positive feedback loop to regulate Hh signaling. In human glioblastoma specimens, the expression levels of USP48 and Gli1 proteins are clinically relevant, and high expression of USP48 correlates with glioma malignancy. In summary, our study reveals that the USP48-Gli1 regulatory axis is critical for glioma cell proliferation and glioblastoma tumorigenesis.
机译：刺猬（HH）信号通路的异常激活驱动多种癌症的肿瘤引发。在这项研究中，我们筛选了一个可以调节HH途径的氘蛋白酶组。我们发现脱硫酶USP48通过稳定Gli1蛋白激活Gli依赖性转录。机械地，USP48与GLI1相互作用，直接切断其泛素。在胶质母细胞中，USP48的敲低抑制细胞增殖和GLI1下游靶标的表达，这导致压抑的胶质母细胞瘤肿瘤发生。重要的是，USP48对细胞增殖和肿瘤引发的影响取决于GLI1的一定程度。此外，我们发现Sonic Hedgehog（SHH）途径通过GLI1介导的转录激活诱导USP48表达，从而形成阳性反馈回路以调节HH信号。在人胶质母细胞瘤样本中，USP48和GLI1蛋白的表达水平在临床相关，USP48的高表达与胶质瘤恶性肿瘤相关。总之，我们的研究表明，USP48-GLI1调节轴对于胶质瘤细胞增殖和胶质母细胞瘤肿瘤内酯至关重要。

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  • 来源
    《EMBO reports》 |2017年第8期|共13页
  • 作者

    Zhou Aidong; Lin Kangyu; Zhang Sicong; Ma Li; Xue Jianfei; Morris Saint-Aaron; Aldape Kenneth D.; Huang Suyun;

  • 作者单位

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Univ Hlth Network MacFeeters Hamilton Ctr Neurooncol Res Princess Margaret Canc Ctr Toronto ON Canada;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    deubiquitination; Gli1; glioblastoma; Hedgehog; USP48;

    机译：脱硫;gli1;gli1;glioblastoma;刺猬;USP48;

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