title: Inhibition of H3K18 deacetylation of Sirt7 by Myb-binding protein 1a (Mybbp1a).
abstract: Sirt7 localizes in the nucleus (enriched in the nucleolus) and is an NAD(+)-dependent deacetylase with high selectivity for the acetylated lysine 18 of histone H3 (H3K18Ac). It has been reported that Sirt7 is necessary for maintaining the fundamental properties of the cancer cell phenotype and stabilizing the tumorigenicity of human cancer via deacetylation of H3K18Ac. However, the regulators of Sirt7 deacetylase activity are unknown. Myb-binding protein 1a (Mybbp1a) is reported to interact with and regulate the function of a number of transcription factors. In the present study, we demonstrated that Mybbp1a binds to Sirt7 in vitro and in vivo. Serial deletion studies indicated that N- and C-terminal regions of Sirt7 and C-terminal region of Mybbp1a are important for the binding. Furthermore, transfection experiments showed that Mybbp1a is capable of inhibiting the deacetylation activity of H3K18Ac by Sirt7. Our findings demonstrate that Mybbp1a is a novel negative regulator of Sirt7.
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Md Fazlul
authors.initials: MF
authors.lastname: Karim
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D037761:Sirtuins / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006657:Histones; C491719:MYBBP1A protein, human; C110421:Mybbp1a protein, mouse; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; C539736:Sirt7 protein, mouse; D014157:Transcription Factors; D037761:Sirtuins; D008239:Lysine
keywords: Acetylation; H3K18; Mybbp1a; Sirt7; Sirtuin