Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Korea.
Department of Cell biology, College of Medicine, Konyang University, Daejeon, Korea.
FEBS Open Bio. 2020 May;10(5):937-950. doi: 10.1002/2211-5463.12855. Epub 2020 Apr 14.
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.
PDZ 结合激酶 (PBK) 先前已被证明能够介导癌细胞对抗癌药物的耐药性。然而，PBK 如何调节紫杉醇诱导的癌细胞死亡仍不清楚。在这里，我们证明 PBK 阻碍了 H460 非小细胞肺癌细胞中紫杉醇介导的自噬细胞死亡。PBK 敲低增加了紫杉醇处理后的细胞凋亡、自噬、p53 水平和 LC3 斑点。此外，p53 表达促进了紫杉醇诱导的 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，紫杉醇诱导 PBK 介导的 p53 核输出及其随后在对照细胞中的泛素化，但在 PBK 敲低细胞中则没有。我们的结论是，PBK 通过抑制 p53 来阻碍紫杉醇诱导的自噬细胞死亡，这表明 PBK 在 p53 介导的 H460 细胞死亡中可能发挥作用。
