Protein kinase A regulates ferroptosis by controlling GPX4 m(6)A modification through phosphorylation of ALKBH5

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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 Name:	Zhao, X., Sun, Y., Zou, J., Wu, Y., Huang, M., Kong, H., Liu, G., Gerhardt, H., Gu, W., Zhang, Y., Shang, M. and Wang, X.
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.
Source:	Cell Death and Differentiation
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Date:	3 February 2025
Official Publication:	https://doi.org/10.1038/s41418-025-01453-3
PubMed:	View item in PubMed

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