title: Acetylation/deacetylation modulates the stability of DNA replication licensing factor Cdt1.
abstract: Proper expression of the replication licensing factor Cdt1 is primarily regulated post-translationally by ubiquitylation and proteasome degradation. In a screen to identify novel non-histone targets of histone deacetylases (HDACs), we found Cdt1 as a binding partner for HDAC11. Cdt1 associates specifically and directly with HDAC11. We show that Cdt1 undergoes acetylation and is reversibly deacetylated by HDAC11. In vitro, Cdt1 can be acetylated at its N terminus by the lysine acetyltransferases KAT2B and KAT3B. Acetylation protects Cdt1 from ubiquitylation and subsequent proteasomal degradation. These results extend the list of non-histone acetylated proteins to include a critical DNA replication factor and provide an additional level of complexity to the regulation of Cdt1.
authors.affiliation: Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Glozak
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000737:chemistry; D004261:DNA Replication; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008239:Lysine; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D025801:Ubiquitin; D004247:DNA; D046988:Proteasome Endopeptidase Complex; C462506:HDAC11 protein, human; D006655:Histone Deacetylases; D008239:Lysine