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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-05-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12855 |
| _version_ | 1818891379415187456 |
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| author | Jung‐Hwan Park Sang‐Ah Park Young‐Ju Lee Hwan‐Woo Park Sang‐Muk Oh |
| author_facet | Jung‐Hwan Park Sang‐Ah Park Young‐Ju Lee Hwan‐Woo Park Sang‐Muk Oh |
| author_sort | Jung‐Hwan Park |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T17:39:52Z |
| format | Article |
| id | doaj.art-ccc1e5c1b64d4b0bbb54afb8d2c3be35 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-19T17:39:52Z |
| publishDate | 2020-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-ccc1e5c1b64d4b0bbb54afb8d2c3be352022-12-21T20:12:15ZengWileyFEBS Open Bio2211-54632020-05-0110593795010.1002/2211-5463.12855PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cellsJung‐Hwan Park0Sang‐Ah Park1Young‐Ju Lee2Hwan‐Woo Park3Sang‐Muk Oh4Department of Biochemistry College of Medicine Konyang University Daejeon KoreaDepartment of Biochemistry College of Medicine Konyang University Daejeon KoreaDepartment of Biochemistry College of Medicine Konyang University Daejeon KoreaDepartment of Cell biology College of Medicine Konyang University Daejeon KoreaDepartment of Biochemistry College of Medicine Konyang University Daejeon KoreaPDZ‐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.https://doi.org/10.1002/2211-5463.12855Mdm2non‐small‐cell lung cancer cellsp53PBKubiquitination |
| spellingShingle | Jung‐Hwan Park Sang‐Ah Park Young‐Ju Lee Hwan‐Woo Park Sang‐Muk Oh PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells FEBS Open Bio Mdm2 non‐small‐cell lung cancer cells p53 PBK ubiquitination |
| title | PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells |
| title_full | PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells |
| title_fullStr | PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells |
| title_full_unstemmed | PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells |
| title_short | PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells |
| title_sort | pbk attenuates paclitaxel induced autophagic cell death by suppressing p53 in h460 non small cell lung cancer cells |
| topic | Mdm2 non‐small‐cell lung cancer cells p53 PBK ubiquitination |
| url | https://doi.org/10.1002/2211-5463.12855 |
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