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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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Autores principales: Park, Jung‐Hwan, Park, Sang‐Ah, Lee, Young‐Ju, Park, Hwan‐Woo, Oh, Sang‐Muk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193173/
https://www.ncbi.nlm.nih.gov/pubmed/32237067
http://dx.doi.org/10.1002/2211-5463.12855
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author Park, Jung‐Hwan
Park, Sang‐Ah
Lee, Young‐Ju
Park, Hwan‐Woo
Oh, Sang‐Muk
author_facet Park, Jung‐Hwan
Park, Sang‐Ah
Lee, Young‐Ju
Park, Hwan‐Woo
Oh, Sang‐Muk
author_sort Park, Jung‐Hwan
collection PubMed
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.
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spelling pubmed-71931732020-05-01 PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells Park, Jung‐Hwan Park, Sang‐Ah Lee, Young‐Ju Park, Hwan‐Woo Oh, Sang‐Muk FEBS Open Bio Research Articles 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. John Wiley and Sons Inc. 2020-04-14 /pmc/articles/PMC7193173/ /pubmed/32237067 http://dx.doi.org/10.1002/2211-5463.12855 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Park, Jung‐Hwan
Park, Sang‐Ah
Lee, Young‐Ju
Park, Hwan‐Woo
Oh, Sang‐Muk
PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells
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 Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193173/
https://www.ncbi.nlm.nih.gov/pubmed/32237067
http://dx.doi.org/10.1002/2211-5463.12855
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