1. ARMS-NF-κB signaling regulates intracellular ROS to induce autophagy-associated cell death upon oxidative stress.
- Author
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Liao YH, Wu JT, Hsieh IC, Lee HH, and Huang PH
- Abstract
Ankyrin repeat-rich membrane spanning (ARMS) plays roles in neural development, neuropathies, and tumor formation. Such pleiotropic function of ARMS is often attributed to diverse ARMS-interacting molecules in different cell context. However, it might be achieved by ARMS' effect on global biological mediator like reactive oxygen species (ROS). We established ARMS -knockdown in melanoma cells (si ARMS ) and in Drosophila eyes ( GMR>dARMS
RNAi ) and challenged them with H2 O2 . Decreased ARMS in both systems compromises nuclear translocation of NF-κB and induces ROS, which in turn augments autophagy flux and confers susceptibility to H2 O2 -triggered autophagic cell death. Resuming NF-κB activity or reducing ROS by antioxidants in si ARMS cells and GMR>dARMSRNAi fly decreases intracellular peroxides level concurrent with reduced autophagy and attenuated cell death. Conversely, blocking NF-κB activity in wild-type flies/melanoma enhances ROS and induces autophagy with cell death. We thus uncover intracellular ROS modulated by ARMS-NFκB signaling primes autophagy for autophagic cell death upon oxidative stress., Competing Interests: We report no potential conflict of interest., (© 2023 The Author(s).)- Published
- 2023
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