METTL16 deficiency attenuates apoptosis through translational control of extrinsic death receptor during nutrient deprivation
Copyright © 2024 Elsevier Inc. All rights reserved..
METTL16 is a well-characterized m6A methyltransferase that has been reported to contribute to tumorigenesis in various types of cancer. However, the effect of METTL16 on tumor progression under restricted nutrient conditions, which commonly occur in tumor microenvironment, has yet to be elucidated. Herein, our study initially reported the inhibitory effect of METTL16 depletion on apoptosis under amino acid starvation conditions. Mechanistically, we determined that the METTL16 knockdown represses the expression of extrinsic death receptors at both transcription and translation levels. Depletion of METTL16 prevented protein synthesis of GCN2, resulting in diminished ATF4 expression in a GCN2-eIF2α-dependent manner. Reduction of ATF4 further declined the expression of apoptotic receptor protein DR5. Meanwhile, METTL16 deficiency directly hampered protein synthesis of FADD and DR5, thereby impairing apoptosis and promoting cancer cell survival. Taken together, our study provides novel evidence for the involvement of METTL16 in regulating cancer progression, suggesting that METTL16 as a potential therapeutic target for cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:708 |
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| Enthalten in: |
Biochemical and biophysical research communications - 708(2024) vom: 14. Apr., Seite 149802 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Qiujie [VerfasserIn] |
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| Links: |
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| Themen: |
Amino Acids |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2024.149802 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a METTL16 deficiency attenuates apoptosis through translational control of extrinsic death receptor during nutrient deprivation |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a METTL16 is a well-characterized m6A methyltransferase that has been reported to contribute to tumorigenesis in various types of cancer. However, the effect of METTL16 on tumor progression under restricted nutrient conditions, which commonly occur in tumor microenvironment, has yet to be elucidated. Herein, our study initially reported the inhibitory effect of METTL16 depletion on apoptosis under amino acid starvation conditions. Mechanistically, we determined that the METTL16 knockdown represses the expression of extrinsic death receptors at both transcription and translation levels. Depletion of METTL16 prevented protein synthesis of GCN2, resulting in diminished ATF4 expression in a GCN2-eIF2α-dependent manner. Reduction of ATF4 further declined the expression of apoptotic receptor protein DR5. Meanwhile, METTL16 deficiency directly hampered protein synthesis of FADD and DR5, thereby impairing apoptosis and promoting cancer cell survival. Taken together, our study provides novel evidence for the involvement of METTL16 in regulating cancer progression, suggesting that METTL16 as a potential therapeutic target for cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amino acid starvation | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Extrinsic death receptor | |
| 650 | 4 | |a METTL16 | |
| 650 | 4 | |a Translation | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a Receptors, Death Domain |2 NLM | |
| 650 | 7 | |a METTL16 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 700 | 1 | |a Yang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chenxin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Jingying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jun |e verfasserin |4 aut | |
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