title: Two distinct nuclear localization signals in mammalian MSL1 regulate its function.
abstract: MSL1 protein regulates global histone H4 acetylation at residue K16 in stem and cancer cells, through interaction with KAT8. The functional significance of mammalian MSL1 isoforms, involved in various protein interactions, is poorly understood. We report the identification of a novel nuclear localization signal (NLS), common to all MSL1 isoforms, in addition to previously known bipartite NLS, located in domain PEHE. Isoforms having both NLS localize to sub-nuclear foci where they can target co-chaperone protein TTC4. However, all MSL1 isoforms also have ability to affect H4K16 acetylation. Thus, presence of two NLS in MSL1 protein can mediate activity of KAT8 in vivo.
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10, Miklukho-Maklaya, 117997, Moscow, Russia.
authors.forename: Ruslan I
authors.initials: RI
authors.lastname: Dmitriev
authors.forename: Nikolay B
authors.initials: NB
authors.lastname: Pestov
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Shakhparonov
authors.forename: Irina A
authors.initials: IA
authors.lastname: Okkelman
mesh_terms: D000107:Acetylation; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D019913:Nuclear Localization Signals; D020033:Protein Isoforms; C417403:TTC4 protein, human; C000602287:TTC4 protein, mouse; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human; C544740:MSL1 protein, human; C557014:MSL1 protein, mouse
keywords: HISTONE ACETYLATION; KAT8; MSL1; NUCLEUS; SUB-NUCLEAR LOCALIZATION