title: Cutting edge: tubulin α functions as an adaptor in NFAT-importin β interaction.
abstract: Upon T cell stimulation, NFAT is dephosphorylated by calcineurin, leading to nuclear translocation via NFAT-importin β interaction. Whereas the process of NFAT dephosphorylation has been well researched, the molecular mechanism of NFAT-importin β interaction remains unknown. In contrast to NF-κB and STAT, no importin α family members have been reported as adaptor proteins for NFAT. Our study shows that tubulin α, but not tubulin β, binds to the N-terminal region of NFAT containing the regulatory and Rel homology domains. Importin β interacts with the NFAT-tubulin α complex rather than NFAT or tubulin α alone, resulting in cotranslocation of NFAT and tubulin α into the nucleus. Furthermore, the interaction is suppressed by acetate-induced tubulin α acetylation at lysine 40. In conclusion, tubulin α functions as an adaptor in NFAT-importin β interaction, and this function is regulated by acetate-induced acetylation.
authors.affiliation: Department of Molecular Biology and Pathogenesis of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000107:Acetylation / Q000187:drug effects; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D019169:Jurkat Cells; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D019346:Sodium Acetate / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism / Q000502:physiology*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C424166:KPNB1 protein, human; D046912:Multiprotein Complexes; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D020033:Protein Isoforms; D014404:Tubulin; D028961:beta Karyopherins; C012589:trichostatin A; D019346:Sodium Acetate; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases