title: Suppression of centrosome duplication and amplification by deacetylases.
abstract: Centrosome duplication is controlled both negatively and positively by a number of proteins. The activities and stabilities of those regulatory proteins are in many cases controlled by posttranslational modifications. Although acetylation and deacetylation are highly common posttranslational modifications, their roles in the regulation of centrosome duplication had not been closely examined. Here, through focusing on the deacetylases, we investigated the role of acetylation/deacetylation in the regulation of centrosome duplication and induction of abnormal amplification of centrosomes. We found that the deacetylation event negatively controls centrosome duplication and amplification. Of the 18 total known deacetylases (HDAC1-11, SIRT1-7), ten deacetylases possess the activity to suppress centrosome amplification, and their centrosome amplification suppressing activities are strongly associated with their abilities to localize to centrosomes. Among them, HDAC1, HDAC5 and SIRT1 show the highest suppressing activities, but each of them suppresses centrosome duplication and/or amplification with its unique mechanism.
authors.affiliation: Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Ling
authors.forename: Lirong
authors.initials: L
authors.lastname: Peng
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukasawa
mesh_terms: D000107:Acetylation; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D019925:Cyclin A; D006657:Histones; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases