title: A novel acetylation of β-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation.
abstract: Dynamic instability is a critical property of microtubules (MTs). By regulating the rate of tubulin polymerization and depolymerization, cells organize the MT cytoskeleton to accommodate their specific functions. Among many processes, posttranslational modifications of tubulin are implicated in regulating MT functions. Here we report a novel tubulin acetylation catalyzed by acetyltransferase San at lysine 252 (K252) of β-tubulin. This acetylation, which is also detected in vivo, is added to soluble tubulin heterodimers but not tubulins in MTs. The acetylation-mimicking K252A/Q mutants were incorporated into the MT cytoskeleton in HeLa cells without causing any obvious MT defect. However, after cold-induced catastrophe, MT regrowth is accelerated in San-siRNA cells while the incorporation of acetylation-mimicking mutant tubulins is severely impeded. K252 of β-tubulin localizes at the interface of α-/β-tubulins and interacts with the phosphate group of the α-tubulin-bound GTP. We propose that the acetylation slows down tubulin incorporation into MTs by neutralizing the positive charge on K252 and allowing tubulin heterodimers to adopt a conformation that disfavors tubulin incorporation.
authors.affiliation: Departments of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Chu
authors.forename: Fajian
authors.initials: F
authors.lastname: Hou
authors.forename: Junmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Lilian
authors.initials: L
authors.lastname: Phu
authors.forename: Alex V
authors.initials: AV
authors.lastname: Loktev
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kirkpatrick
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D058105:Polymerization; D011499:Protein Processing, Post-Translational / Q000235:genetics; D014404:Tubulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D014404:Tubulin; D000123:Acetyltransferases