ArticleMolecular biology of the cell2003
p38 Mitogen-activated protein kinase mediates cell death and p21-activated kinase mediates cell survival during chemotherapeutic drug-induced mitotic arrest.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 164 citations in OpenAlex.
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- ROS production by mitochondria: function or dysfunction?Oncogene · 2024Review
- Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment.Cancers · 2023Review
- Apoptotic Effect of Gallic Acid via Regulation of p-p38 and ER Stress in PANC-1 and MIA PaCa-2 Cells Pancreatic Cancer Cells.International journal of molecular sciences · 2023Article
- Mad2B forms a complex with Cdc20, Cdc27, Rev3 and Rev1 in response to cisplatin-induced DNA damage.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage.Biomolecules & therapeutics · 2023Article
- The functional role of p38 MAPK pathway in malignant brain tumors.Frontiers in pharmacology · 2022Review
- Venlafaxine, an anti-depressant drug, induces apoptosis in MV3 human melanoma cells through JNK1/2-Nur77 signaling pathway.Frontiers in pharmacology · 2022Article
- Editorial: Chemo-Resistance in Gastrointestinal Cancers.Frontiers in oncology · 2022Article
- Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways.Biomolecules · 2021Review
- Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML.Cell death discovery · 2021Article
- Ginaton injection alleviates cisplatin-induced renal interstitial fibrosis in rats via inhibition of apoptosis through regulation of the p38MAPK/TGF-β1 and p38MAPK/HIF-1α pathways.Biomedical reports · 2021Article
- MAPK signaling pathway-targeted marine compounds in cancer therapy.Journal of cancer research and clinical oncology · 2021Review
- Liposomes Targeting P21 Activated Kinase-1 (PAK-1) and Selective for Secretory Phospholipase AInternational journal of molecular sciences · 2020Article
- Liriopesides B induces apoptosis and cell cycle arrest in human non‑small cell lung cancer cells.International journal of molecular medicine · 2020Article
- Review
- Pds5A and Pds5B Display Non-redundant Functions in Mitosis and Their Loss Triggers Chk1 Activation.Frontiers in cell and developmental biology · 2020Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the mitotic checkpoint by chemotherapeutic drugs such as taxol causes mammalian cells to arrest in mitosis and then undergo apoptosis. However, the biochemical basis of chemotherapeutic drug-induced cell death is unclear. Herein, we provide new evidence that both cell survival and cell death-signaling pathways are concomitantly activated during mitotic arrest by microtubule-interfering drugs. Treatment of HeLa cells with chemotherapeutic drugs activated both p38 mitogen-activated protein kinase (MAPK) and p21-activated kinase (PAK). p38 MAPK was necessary for chemotherapeutic drug-induced cell death because the p38 MAPK inhibitors SB203580 or SB202190 suppressed cell death. Dominant-active MKK6, a direct activator of p38 MAPK, also induced cell death by stimulating translocation of Bax from the cytosol to the mitochondria in a p38 MAPK-dependent manner. Dominant active PAK suppressed this MKK6-induced cell death. PAK seems to mediate cell survival by phosphorylating Bad, and inhibition of PAK in mitotically arrested cells reduced Bad phosphorylation and increased apoptosis. Our results suggest that therapeutic strategies that suppress PAK-mediated survival signals may improve the efficacy of current cancer chemotherapies by enhancing p38 MAPK-mediated cell death.
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