PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

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‐cel...

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Bibliographic Details
Published in:FEBS open bio 2020-05, Vol.10 (5), p.937-950
Main Authors: Park, Jung‐Hwan, Park, Sang‐Ah, Lee, Young‐Ju, Park, Hwan‐Woo, Oh, Sang‐Muk
Format: Article
Language:English
Subjects:
Antineoplastic drugs
Antitumor agents
Apoptosis
Autophagy
Cancer therapies
Cell cycle
Cell death
Cervical cancer
Chemoresistance
Flow cytometry
Immunoglobulins
Kinases
Lung cancer
Mdm2
Microscopy
non‐small‐cell lung cancer cells
Nuclear transport
p53
p53 Protein
Paclitaxel
PBK
Phagocytosis
Plasmids
Proteins
Statistical analysis
Transcription
Ubiquitination
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Summary: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. When PDZ‐binding kinase (PBK) is present (B), PBK interacts with p53 in the nucleus and then translocates to the cytoplasm upon paclitaxel treatment, leading to Mdm2‐mediated p53 ubiquitination and subsequent degradation, which induces a decrease in p53‐mediated apoptosis or autophagy in H460 non‐small‐cell lung cancer cells. In contrast, p53‐mediated apoptosis and autophagy are markedly promoted in the absence of PBK (A).
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12855