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Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis

Elevated levels of NF-κB are frequently detected in many inflammatory diseases and cancers. Blocking the IKK–NF-κB pathway has been seen as a promising approach for new therapies. By employing the dominant-negative mutant of IKKβ, our data revealed that loss of IKKβ activity reduces not only the pro...

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Autores principales: Yang, Pei-Ming, Huang, Wei-Chien, Lin, Yi-Chu, Huang, Wen-Yu, Wu, Hui-Ann, Chen, Wei-Lun, Chang, Yu-Fan, Chou, Chia-Wei, Tzeng, Cherng-Chyi, Chen, Yeh-Long, Chen, Ching-Chow
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823466/
https://www.ncbi.nlm.nih.gov/pubmed/19243472
http://dx.doi.org/10.1111/j.1582-4934.2009.00712.x
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author Yang, Pei-Ming
Huang, Wei-Chien
Lin, Yi-Chu
Huang, Wen-Yu
Wu, Hui-Ann
Chen, Wei-Lun
Chang, Yu-Fan
Chou, Chia-Wei
Tzeng, Cherng-Chyi
Chen, Yeh-Long
Chen, Ching-Chow
author_facet Yang, Pei-Ming
Huang, Wei-Chien
Lin, Yi-Chu
Huang, Wen-Yu
Wu, Hui-Ann
Chen, Wei-Lun
Chang, Yu-Fan
Chou, Chia-Wei
Tzeng, Cherng-Chyi
Chen, Yeh-Long
Chen, Ching-Chow
author_sort Yang, Pei-Ming
collection PubMed
description Elevated levels of NF-κB are frequently detected in many inflammatory diseases and cancers. Blocking the IKK–NF-κB pathway has been seen as a promising approach for new therapies. By employing the dominant-negative mutant of IKKβ, our data revealed that loss of IKKβ activity reduces not only the proliferation and invasion of lung adenocarcinoma A549 cells in vitro but also the tumour formation, metastasis and angiogenesis in mouse xenograft model. Treatment of IKKβ inhibitors (CYL-19s and CYL-26z) leads to the arrest of cell cycle progression at G1 and G2/M, followed by apoptosis. IKKβ inhibitors can increase the protein stability, nuclear accumulation and promoter-binding activity of p53, leading to the p21 gene transcription. Furthermore, knockdown of IKKβ by siRNA increased the stability and expression of p53 and p21 promoter activity. In addition, IKKβ inhibitor–induced p53 and p21 expressions were augmented in the presence of IKKβ siRNA. Correlation between p53 acetylation and its protein stabilization was also seen after treatment with IKKβ inhibitors. These results suggest that loss of IKKβ activation is important for the enhancement of p53 stability, leading to p21 expression and cell cycle arrest and apoptosis of tumour cells.
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spelling pubmed-38234662015-04-20 Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis Yang, Pei-Ming Huang, Wei-Chien Lin, Yi-Chu Huang, Wen-Yu Wu, Hui-Ann Chen, Wei-Lun Chang, Yu-Fan Chou, Chia-Wei Tzeng, Cherng-Chyi Chen, Yeh-Long Chen, Ching-Chow J Cell Mol Med Articles Elevated levels of NF-κB are frequently detected in many inflammatory diseases and cancers. Blocking the IKK–NF-κB pathway has been seen as a promising approach for new therapies. By employing the dominant-negative mutant of IKKβ, our data revealed that loss of IKKβ activity reduces not only the proliferation and invasion of lung adenocarcinoma A549 cells in vitro but also the tumour formation, metastasis and angiogenesis in mouse xenograft model. Treatment of IKKβ inhibitors (CYL-19s and CYL-26z) leads to the arrest of cell cycle progression at G1 and G2/M, followed by apoptosis. IKKβ inhibitors can increase the protein stability, nuclear accumulation and promoter-binding activity of p53, leading to the p21 gene transcription. Furthermore, knockdown of IKKβ by siRNA increased the stability and expression of p53 and p21 promoter activity. In addition, IKKβ inhibitor–induced p53 and p21 expressions were augmented in the presence of IKKβ siRNA. Correlation between p53 acetylation and its protein stabilization was also seen after treatment with IKKβ inhibitors. These results suggest that loss of IKKβ activation is important for the enhancement of p53 stability, leading to p21 expression and cell cycle arrest and apoptosis of tumour cells. Blackwell Publishing Ltd 2010-03 2009-02-20 /pmc/articles/PMC3823466/ /pubmed/19243472 http://dx.doi.org/10.1111/j.1582-4934.2009.00712.x Text en © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Articles
Yang, Pei-Ming
Huang, Wei-Chien
Lin, Yi-Chu
Huang, Wen-Yu
Wu, Hui-Ann
Chen, Wei-Lun
Chang, Yu-Fan
Chou, Chia-Wei
Tzeng, Cherng-Chyi
Chen, Yeh-Long
Chen, Ching-Chow
Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title_full Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title_fullStr Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title_full_unstemmed Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title_short Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
title_sort loss of ikkβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823466/
https://www.ncbi.nlm.nih.gov/pubmed/19243472
http://dx.doi.org/10.1111/j.1582-4934.2009.00712.x
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