Deregulated JNK signaling enhances apoptosis during hyperthermia
Purpose c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown. The aim of this study was to clarify...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | International Journal of Hyperthermia |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/02656736.2024.2335199 |
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| author | Atsushi Enomoto Takemichi Fukasawa Hiroshi Terunuma Keiichi Nakagawa Ayumi Yoshizaki Shinichi Sato Noriko Hosoya Kiyoshi Miyagawa |
| author_facet | Atsushi Enomoto Takemichi Fukasawa Hiroshi Terunuma Keiichi Nakagawa Ayumi Yoshizaki Shinichi Sato Noriko Hosoya Kiyoshi Miyagawa |
| author_sort | Atsushi Enomoto |
| collection | DOAJ |
| description | Purpose c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown. The aim of this study was to clarify how JNK activity is stimulated by heat.Methods and materials The expression levels of various MAPK members in HeLa cells, with or without hyperthermia treatment, were evaluated via western blotting. The kinase activity of MAPK members was assessed through in vitro kinase assays. Cell death was assessed in the absence or presence of siRNAs targeting MAPK-related members.Results Hyperthermia decreased the levels of MAP3Ks, such as ASK1 and MLK3 which are JNK kinase kinase members, but not those of the downstream MAP2K/SEK1 and MAPK/JNK. Despite the reduced or transient phosphorylation of ASK1, MLK3, or SEK1, downstream JNK was phosphorylated in a temperature-dependent manner. In vitro kinase assays demonstrated that heat did not directly stimulate SEK1 or JNK. However, the expression levels of DUSP16, a JNK phosphatase, were decreased upon hyperthermia treatment. DUSP16 knockdown enhanced the heat-induced activation of ASK1–SEK1–JNK pathway and apoptosis.Conclusion JNK was activated in a temperature-dependent manner despite reduced or transient phosphorylation of the upstream MAP3K and MAP2K. Hyperthermia-induced degradation of DUSP16 may induce activation of the ASK1–SEK1–JNK pathway and subsequent apoptosis. |
| format | Article |
| id | doaj-art-9386758602e74631bb78906ebd21bea5 |
| institution | Kabale University |
| issn | 0265-6736 1464-5157 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj-art-9386758602e74631bb78906ebd21bea52025-01-03T09:30:27ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572024-12-0141110.1080/02656736.2024.2335199Deregulated JNK signaling enhances apoptosis during hyperthermiaAtsushi Enomoto0Takemichi Fukasawa1Hiroshi Terunuma2Keiichi Nakagawa3Ayumi Yoshizaki4Shinichi Sato5Noriko Hosoya6Kiyoshi Miyagawa7Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanMedical Oncology, Tokyo Clinic, Tokyo, JapanComprehensive Radiation Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Dermatology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanLaboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanLaboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanPurpose c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown. The aim of this study was to clarify how JNK activity is stimulated by heat.Methods and materials The expression levels of various MAPK members in HeLa cells, with or without hyperthermia treatment, were evaluated via western blotting. The kinase activity of MAPK members was assessed through in vitro kinase assays. Cell death was assessed in the absence or presence of siRNAs targeting MAPK-related members.Results Hyperthermia decreased the levels of MAP3Ks, such as ASK1 and MLK3 which are JNK kinase kinase members, but not those of the downstream MAP2K/SEK1 and MAPK/JNK. Despite the reduced or transient phosphorylation of ASK1, MLK3, or SEK1, downstream JNK was phosphorylated in a temperature-dependent manner. In vitro kinase assays demonstrated that heat did not directly stimulate SEK1 or JNK. However, the expression levels of DUSP16, a JNK phosphatase, were decreased upon hyperthermia treatment. DUSP16 knockdown enhanced the heat-induced activation of ASK1–SEK1–JNK pathway and apoptosis.Conclusion JNK was activated in a temperature-dependent manner despite reduced or transient phosphorylation of the upstream MAP3K and MAP2K. Hyperthermia-induced degradation of DUSP16 may induce activation of the ASK1–SEK1–JNK pathway and subsequent apoptosis.https://www.tandfonline.com/doi/10.1080/02656736.2024.2335199HyperthermiadegradationphosphorylationJNK signalingDUSP16apoptosis |
| spellingShingle | Atsushi Enomoto Takemichi Fukasawa Hiroshi Terunuma Keiichi Nakagawa Ayumi Yoshizaki Shinichi Sato Noriko Hosoya Kiyoshi Miyagawa Deregulated JNK signaling enhances apoptosis during hyperthermia International Journal of Hyperthermia Hyperthermia degradation phosphorylation JNK signaling DUSP16 apoptosis |
| title | Deregulated JNK signaling enhances apoptosis during hyperthermia |
| title_full | Deregulated JNK signaling enhances apoptosis during hyperthermia |
| title_fullStr | Deregulated JNK signaling enhances apoptosis during hyperthermia |
| title_full_unstemmed | Deregulated JNK signaling enhances apoptosis during hyperthermia |
| title_short | Deregulated JNK signaling enhances apoptosis during hyperthermia |
| title_sort | deregulated jnk signaling enhances apoptosis during hyperthermia |
| topic | Hyperthermia degradation phosphorylation JNK signaling DUSP16 apoptosis |
| url | https://www.tandfonline.com/doi/10.1080/02656736.2024.2335199 |
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