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| Item Type: | Article |
|---|---|
| Title: | Protein kinase A regulates ferroptosis by controlling GPX4 m(6)A modification through phosphorylation of ALKBH5 |
| Creators: |
Zhao, X.  ORCID: https://orcid.org/0000-0002-4048-6813, Sun, Y. ORCID: https://orcid.org/0009-0005-8556-356X, Zou, J., Wu, Y., Huang, M., Kong, H., Liu, G., Gerhardt, H. ORCID: https://orcid.org/0000-0002-3030-0384, Gu, W. ORCID: https://orcid.org/0000-0002-1480-2368, Zhang, Y. ORCID: https://orcid.org/0000-0002-6465-7488, Shang, M. ORCID: https://orcid.org/0000-0003-4511-4290 and Wang, X. ORCID: https://orcid.org/0000-0002-2457-8726
|
| Abstract: | GPX4-dependent ferroptosis has emerged as a therapeutic strategy for cancer treatment. Here, we demonstrated that protein kinase A (PKA) participates in the regulation of ferroptosis by controlling the m(6)A modification of GPX4 in an ALKBH5-dependent manner. Notably, we identified ALKBH5, an m(6)A demethylase, as a novel target of PKA, which drives phosphorylation-dependent degradation of ALKBH5 protein. Moreover, the deletion of ALKBH5 represses ferroptotic cell death by maintaining GPX4 m(6)A modification and stability. Thus, by regulating ALKBH5-dependent GPX4 stability, PKA acts as a key regulator of ferroptosis. Our study unveils the involvement of PKA in m(6)A modification, which could control GPX4-dependent ferroptosis and tumor progression. |
| Keywords: | Cyclic AMP-Dependent Protein Kinases, Ferroptosis, HEK293 Cells, Phospholipid Hydroperoxide Glutathione Peroxidase, Phosphorylation, RNA Demethylase AlkB Homolog 5, Animals, Mice |
| Source: | Cell Death and Differentiation |
| ISSN: | 1350-9047 |
| Publisher: | Nature Publishing Group |
| Volume: | 32 |
| Number: | 6 |
| Page Range: | 1617 |
| Date: | June 2025 |
| Official Publication: | https://doi.org/10.1038/s41418-025-01453-3 |
| PubMed: | View item in PubMed |
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