Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 17, Pages 11816-11828Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.507400
Keywords
AMP-activated Kinase (AMPK); Microtubules; p300; Reactive Oxygen Species (ROS); Stress; Tubulin; AMPK; MEC-17; ATAT1; Acetylation
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Funding
- Ministere de l'Enseignement Superieur et de la Recherche [EA 4530]
- INSERM [U845]
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Background: Tubulin acetylation is a hallmark of microtubule stabilization, which may modulate the binding of microtubule-associated proteins. Results: Microtubules are hyperacetylated because of stress-induced cellular signaling upstream of the tubulin acetyltransferase MEC-17/TAT1. Conclusion: MEC-17/TAT1 is regulated by p300, reactive oxygen species, and AMP-activated protein kinase. Significance: Microtubule hyperacetylation is important for cell adaptation to stress through autophagy induction and for cell survival. Beyond its presence in stable microtubules, tubulin acetylation can be boosted after UV exposure or after nutrient deprivation, but the mechanisms of microtubule hyperacetylation are still unknown. In this study, we show that this hyperacetylation is a common response to several cellular stresses that involves the stimulation of the major tubulin acetyltransferase MEC-17. We also demonstrate that the acetyltransferase p300 negatively regulates MEC-17 expression and is sequestered on microtubules upon stress. We further show that reactive oxygen species of mitochondrial origin are required for microtubule hyperacetylation by activating the AMP kinase, which in turn mediates MEC-17 phosphorylation upon stress. Finally, we show that preventing microtubule hyperacetylation by knocking down MEC-17 affects cell survival under stress conditions and starvation-induced autophagy, thereby pointing out the importance of this rapid modification as a broad cell response to stress.
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