Tubulin acetylation favors Hsp90 recruitment to microtubules and stimulates the signaling function of the Hsp90 clients Akt/PKB and p53.
Involved in a wide range of cellular processes such as signal transduction, microtubules are highly dynamic polymers that accumulate various post-translational modifications including polyglutamylation, polyglycylation, carboxyterminal cleavage and acetylation, the functions of which just begin to be uncovered. The molecular chaperone Hsp90, which is essential for the folding and activity of numerous client proteins involved in cell proliferation and apoptosis, associates with the microtubule network but the effects of tubulin post-translational modifications on its microtubule binding has not yet been investigated. Herein, we show that both the constitutive (beta) and the inducible (alpha) Hsp90 isoforms bind to microtubules in a way that depends on the level of tubulin acetylation. Tubulin acetylation also stimulates the binding and the signaling function of at least two of its client proteins, the kinase Akt/PKB and the transcription factor p53. This study highlights the role of tubulin acetylation in modulating microtubule-based transport of Hsp90-chaperoned proteins and thus in regulating signaling dynamics in the cytoplasm.
Giustiniani
Julien
J
Laboratoire de Biochimie et Biologie Cellulaire, UPRES JE 2493-IFR141, Univ. Paris-Sud 11, Faculté de Pharmacie, 5 rue J.B. Clément, 92290 Châtenay-Malabry, France.
Daire
Vanessa
V
Cantaloube
Isabelle
I
Durand
Geneviève
G
Poüs
Christian
C
Perdiz
Daniel
D
Baillet
Anita
A
D000107:Acetylation; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000502:physiology*; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D014404:Tubulin / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C012589:trichostatin A; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt