ArticleThe Journal of biological chemistry2014
Induction of p21CIP1 protein and cell cycle arrest after inhibition of Aurora B kinase is attributed to aneuploidy and reactive oxygen species.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- KRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors.NPJ precision oncology · 2026Article
- Article
- Long noncoding RNA,Frontiers in cell and developmental biology · 2024Article
- Multifaceted Effects of Kinase Inhibitors on Pancreatic Cancer Cells Reveals Pivotal Entities with Therapeutic Implications.Biomedicines · 2023Article
- Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas.International journal of molecular sciences · 2023Article
- Piperine-Chlorogenic Acid Hybrid Inhibits the Proliferation of the SK-MEL-147 Melanoma Cells by Modulating Mitotic Kinases.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Karyotype Aberrations in Action: The Evolution of Cancer Genomes and the Tumor Microenvironment.Genes · 2021Review
- Ataxia telangiectasia mutated pathway disruption affects hepatic DNA and tissue damage in nonalcoholic fatty liver disease.Experimental and molecular pathology · 2020Article
- Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.Cell proliferation · 2018Article
- Development of Chemotherapy with Cell-Cycle Inhibitors for Adult and Pediatric Cancer Therapy.Cancer research · 2018Review
- Mitochondria-targeted antioxidant SkQ1 suppresses fibrosarcoma and rhabdomyosarcoma tumour cell growth.Cell cycle (Georgetown, Tex.) · 2018Article
- Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy.The Journal of biological chemistry · 2017Article
- The Role of Aneuploidy in Cancer Evolution.Cold Spring Harbor perspectives in medicine · 2017Review
- Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain.Mechanisms of ageing and development · 2017Review
- Targeted TPX2 increases chromosome missegregation and suppresses tumor cell growth in human prostate cancer.OncoTargets and therapy · 2017Article
- Ku70 Serine 155 mediates Aurora B inhibition and activation of the DNA damage response.Scientific reports · 2016Article
- Whole Chromosome Instability induces senescence and promotes SASP.Scientific reports · 2016Article
- The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer.Cancer biology & therapy · 2016Article
- Aurora B Overexpression Causes Aneuploidy and p21Cip1 Repression during Tumor Development.Molecular and cellular biology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell cycle progression requires a series of highly coordinated events that ultimately lead to faithful segregation of chromosomes. Aurora B is an essential mitotic kinase, which is involved in regulation of microtubule-kinetochore attachments and cytokinesis. Inhibition of Aurora B results in stabilization of p53 and induction of p53-target genes such as p21 to inhibit proliferation. We have previously demonstrated that induction of p21 by p53 after inhibition of Aurora B is dependent on the p38 MAPK, which promotes transcriptional elongation of p21 by RNA Pol II. In this study, we show that a subset of p53-target genes are induced in a p38-dependent manner upon inhibition of Aurora B. We also demonstrate that inhibition of Aurora B results in down-regulation of E2F-mediated transcription and that the cell cycle arrest after Aurora B inhibition depends on p53 and pRB tumor suppressor pathways. In addition, we report that activation of p21 after inhibition of Aurora B is correlated with increased chromosome missegregation and aneuploidy but not with binucleation or tetraploidy. We provide evidence that p21 is activated in aneuploid cells by reactive oxygen species (ROS) and p38 MAPK. Finally, we demonstrate that certain drugs that act on aneuploid cells synergize with inhibitors of Aurora B to inhibit colony formation and oncogenic transformation. These findings provide an important link between aneuploidy and the stress pathways activated by Aurora B inhibition and also support the use of Aurora B inhibitors in combination therapy for treatment of cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.