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CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer

Rationale: Radioresistance is considered the main cause of local relapse in lung cancer. However, the molecular mechanisms of radioresistance remain poorly understood. This study investigates the role of CDK16 in radioresistance of human lung cancer cells. Methods: The expression levels of CDK16 wer...

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Autores principales: Xie, Jie, Li, Yan, Jiang, Ke, Hu, Kaishun, Zhang, Sheng, Dong, Xiaorong, Dai, Xiaofang, Liu, Li, Zhang, Tao, Yang, Kunyu, Huang, Kai, Chen, Junjie, Shi, Shaojun, Zhang, Yu, Wu, Gang, Xu, Shuangbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771083/
https://www.ncbi.nlm.nih.gov/pubmed/29344296
http://dx.doi.org/10.7150/thno.21963
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author Xie, Jie
Li, Yan
Jiang, Ke
Hu, Kaishun
Zhang, Sheng
Dong, Xiaorong
Dai, Xiaofang
Liu, Li
Zhang, Tao
Yang, Kunyu
Huang, Kai
Chen, Junjie
Shi, Shaojun
Zhang, Yu
Wu, Gang
Xu, Shuangbing
author_facet Xie, Jie
Li, Yan
Jiang, Ke
Hu, Kaishun
Zhang, Sheng
Dong, Xiaorong
Dai, Xiaofang
Liu, Li
Zhang, Tao
Yang, Kunyu
Huang, Kai
Chen, Junjie
Shi, Shaojun
Zhang, Yu
Wu, Gang
Xu, Shuangbing
author_sort Xie, Jie
collection PubMed
description Rationale: Radioresistance is considered the main cause of local relapse in lung cancer. However, the molecular mechanisms of radioresistance remain poorly understood. This study investigates the role of CDK16 in radioresistance of human lung cancer cells. Methods: The expression levels of CDK16 were determined by immunohistochemistry in lung cancer tissues and adjacent normal lung tissues. Immunoprecipitation assay and GST pulldown were utilized to detect the protein-protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase assay. Poly-ubiquitination of p53 was examined by in vivo ubiquitination assay. Cell growth and apoptosis, ROS levels and DNA damage response were measured for functional analyses. Results: We showed that CDK16 is frequently overexpressed in lung cancer cells and tissues, and high levels of CDK16 are correlated with lymph node stage and poor prognosis in lung cancer patients. Furthermore, we provided evidence that CDK16 binds to and phosphorylates p53 at Ser315 site to inhibit transcriptional activity of p53. Moreover, we uncovered that this phosphorylation modification accelerates p53 degradation via the ubiquitin/proteasome pathway. Importantly, we demonstrated that CDK16 promotes radioresistance by suppressing apoptosis and ROS production as well as inhibiting DNA damage response in lung cancer cells in a p53-dependent manner. Conclusion: Our findings suggest that CDK16 negatively modulates p53 signaling pathway to promote radioresistance, and therefore represents a promising therapeutic target for lung cancer radiotherapy.
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spelling pubmed-57710832018-01-17 CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer Xie, Jie Li, Yan Jiang, Ke Hu, Kaishun Zhang, Sheng Dong, Xiaorong Dai, Xiaofang Liu, Li Zhang, Tao Yang, Kunyu Huang, Kai Chen, Junjie Shi, Shaojun Zhang, Yu Wu, Gang Xu, Shuangbing Theranostics Research Paper Rationale: Radioresistance is considered the main cause of local relapse in lung cancer. However, the molecular mechanisms of radioresistance remain poorly understood. This study investigates the role of CDK16 in radioresistance of human lung cancer cells. Methods: The expression levels of CDK16 were determined by immunohistochemistry in lung cancer tissues and adjacent normal lung tissues. Immunoprecipitation assay and GST pulldown were utilized to detect the protein-protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase assay. Poly-ubiquitination of p53 was examined by in vivo ubiquitination assay. Cell growth and apoptosis, ROS levels and DNA damage response were measured for functional analyses. Results: We showed that CDK16 is frequently overexpressed in lung cancer cells and tissues, and high levels of CDK16 are correlated with lymph node stage and poor prognosis in lung cancer patients. Furthermore, we provided evidence that CDK16 binds to and phosphorylates p53 at Ser315 site to inhibit transcriptional activity of p53. Moreover, we uncovered that this phosphorylation modification accelerates p53 degradation via the ubiquitin/proteasome pathway. Importantly, we demonstrated that CDK16 promotes radioresistance by suppressing apoptosis and ROS production as well as inhibiting DNA damage response in lung cancer cells in a p53-dependent manner. Conclusion: Our findings suggest that CDK16 negatively modulates p53 signaling pathway to promote radioresistance, and therefore represents a promising therapeutic target for lung cancer radiotherapy. Ivyspring International Publisher 2018-01-01 /pmc/articles/PMC5771083/ /pubmed/29344296 http://dx.doi.org/10.7150/thno.21963 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Xie, Jie
Li, Yan
Jiang, Ke
Hu, Kaishun
Zhang, Sheng
Dong, Xiaorong
Dai, Xiaofang
Liu, Li
Zhang, Tao
Yang, Kunyu
Huang, Kai
Chen, Junjie
Shi, Shaojun
Zhang, Yu
Wu, Gang
Xu, Shuangbing
CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title_full CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title_fullStr CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title_full_unstemmed CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title_short CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer
title_sort cdk16 phosphorylates and degrades p53 to promote radioresistance and predicts prognosis in lung cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771083/
https://www.ncbi.nlm.nih.gov/pubmed/29344296
http://dx.doi.org/10.7150/thno.21963
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