PML 和 PML-RARα 对 NF-κB 的调节。
Regulation of NF-κB by PML and PML-RARα.
机构信息
Department of Biochemistry, University College Cork, Cork, Ireland.
Shenzhen Institutes of Advanced Technology, Shenzhen, China.
出版信息
Sci Rep. 2017 Mar 20;7:44539. doi: 10.1038/srep44539.
Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB.
早幼粒细胞白血病（PML）是一种核蛋白，它形成核体内的亚核结构，称为与转录活性基因组区域相关的核体。PML 是一种肿瘤抑制因子和细胞分化的调节剂。我们证明 PML 通过促进 NF-κB 活性来促进 TNFα 诱导的转录反应。TNFα 处理的 PML 细胞显示正常的 IκBα 降解和 NF-κB 核易位，但 NF-κB DNA 结合和 NF-κB p65 的磷酸化明显减少。我们还证明，导致急性早幼粒细胞白血病的 PML 维甲酸受体-α（PML-RARα）癌融合蛋白抑制 TNFα 诱导的基因表达和 NF-κB 的磷酸化。这项研究确立了 PML 作为 NF-κB 的重要调节剂，并表明 PML-RARα 失调 NF-κB。
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