PBK attenuates paclitaxel-induced autophagic cell death by suppressing p53 in H460 non-small-cell lung cancer cells.,FEBS Open Bio

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PBK attenuates paclitaxel-induced autophagic cell death by suppressing p53 in H460 non-small-cell lung cancer cells.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-04-14 , DOI: 10.1002/2211-5463.12855
Jung-Hwan Park ₁ , Sang-Ah Park ₁ , Young-Ju Lee ₁ , Hwan-Woo Park ₂ , Sang-Muk Oh _{1,

3}

Affiliation

PDZ‐binding kinase (PBK) has previously been shown to mediate chemoresistance of cancer cells to anticancer drugs. However, it remains unclear how PBK regulates paclitaxel‐induced cancer cell death. Here, we demonstrate that PBK hinders paclitaxel‐mediated autophagic cell death in H460 non‐small‐cell lung cancer cells. PBK knockdown increased apoptosis, autophagy, p53 level, and LC3 puncta upon paclitaxel treatment. Moreover, p53 expression facilitated an increase in the LC3‐II/LC3‐I ratio in response to paclitaxel, and PBK knockdown augmented paclitaxel‐mediated p53 transcriptional activity. Meanwhile, paclitaxel induced PBK‐mediated p53 nuclear export and its subsequent ubiquitination in control cells, but not in PBK knockdown cells. We conclude that PBK hampers paclitaxel‐induced autophagic cell death by suppressing p53, suggesting a potential role of PBK in p53‐mediated H460 cell death.

中文翻译：

PBK通过抑制H460非小细胞肺癌细胞中的p53来减轻紫杉醇诱导的自噬细胞死亡。

以前已经证明PDZ结合激酶（PBK）介导癌细胞对抗癌药物的化学耐药性。但是，尚不清楚PBK如何调节紫杉醇诱导的癌细胞死亡。在这里，我们证明了PBK在H460非小细胞肺癌细胞中阻碍了紫杉醇介导的自噬细胞死亡。紫杉醇治疗后，PBK敲低会增加细胞凋亡，自噬，p53水平和LC3点。此外，p53的表达促进了响应紫杉醇的LC3-II / LC3-I比值的增加，而PBK敲低增强了紫杉醇介导的p53转录活性。同时，紫杉醇在控制细胞中诱导了PBK介导的p53核输出及其随后的泛素化，但在PBK敲低细胞中却没有。我们得出结论，PBK通过抑制p53阻碍了紫杉醇诱导的自噬细胞死亡，

更新日期：2020-04-14

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