title: Reactive oxygen species, AMP-activated protein kinase, and the transcription cofactor p300 regulate α-tubulin acetyltransferase-1 (αTAT-1/MEC-17)-dependent microtubule hyperacetylation during cell stress.
abstract: 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.
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Rafah
authors.initials: R
authors.lastname: Mackeh
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lorin
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Ameetha
authors.initials: A
authors.lastname: Ratier
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Najet
authors.initials: N
authors.lastname: Mejdoubi-Charef
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Baillet
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France; Assistance Publique-Hôpitaux de Paris, Service de Biochimie Métabolique et Cellulaire, Hôpital Bichat, 75018 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bruneel
authors.affiliation: INSERM U845, Université Paris Descartes, 75014 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamaï
authors.affiliation: INSERM U845, Université Paris Descartes, 75014 Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France; Biochimie-Hormonologie, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, 92141 Clamart, France. Electronic address: christian.pous@u-psud.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Poüs
authors.affiliation: Université Paris Sud, EA4530, Faculté de Pharmacie, Châtenay-Malabry, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Perdiz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D018384:Oxidative Stress; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase; D050880:p300-CBP Transcription Factors; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated Kinase (AMPK); AMPK; Acetylation; MEC-17 / ATAT1; Microtubules; Reactive Oxygen Species (ROS); Stress; Tubulin; p300