title: Histone deacetylase 3 regulates cyclin A stability.
abstract: PCAF and GCN5 acetylate cyclin A at specific lysine residues targeting it for degradation at mitosis. We report here that histone deacetylase 3 (HDAC3) directly interacts with and deacetylates cyclin A. HDAC3 interacts with a domain included in the first 171 aa of cyclin A, a region involved in the regulation of its stability. In cells, overexpression of HDAC3 reduced cyclin A acetylation whereas the knocking down of HDAC3 increased its acetylation. Moreover, reduction of HDAC3 levels induced a decrease of cyclin A that can be reversed by proteasome inhibitors. These results indicate that HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome. Interestingly, HDAC3 is abruptly degraded at mitosis also via proteasome thus facilitating cyclin A acetylation by PCAF/GCN5, which will target cyclin A for degradation. Because cyclin A is crucial for S phase progression and mitosis entry, the knock down of HDAC3 affects cell cycle progression specifically at both, S phase and G2/M transition. In summary we propose here that HDAC3 regulates cyclin A stability by counteracting the action of the acetylases PCAF/GCN5.
authors.affiliation: From the Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain and.
authors.forename: Miriam
authors.initials: M
authors.lastname: Vidal-Laliena
authors.affiliation: From the Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain and.
authors.forename: Edurne
authors.initials: E
authors.lastname: Gallastegui
authors.affiliation: the Departments of Cell Biology and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mateo
authors.affiliation: Molecular Biology, Barcelona Institute of Molecular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 08028 Barcelona, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Martínez-Balbás
authors.affiliation: From the Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain and.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Pujol
authors.affiliation: From the Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain and. Electronic address: obachs@ub.edu.
authors.forename: Oriol
authors.initials: O
authors.lastname: Bachs
mesh_terms: D000107:Acetylation; D056750:Cyclin A1 / Q000378:metabolism*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D016196:S Phase; D000099186:Histone Deacetylase 3
chemical_list: D056750:Cyclin A1; D006655:Histone Deacetylases; D046988:Proteasome Endopeptidase Complex; D000099186:Histone Deacetylase 3; C503745:CCNA1 protein, human
keywords: Cell Cycle; Cyclin A; Cyclins; HDAC3; Histone Deacetylase; PCAF; Protein Degradation; Protein Stability