title: Stability of Nmi protein is controlled by its association with Tip60.
abstract: Tip60 exerts diverse biological functions through mechanisms that are either dependent or independent on its intrinsic histone acetyltransferase activity. In the present study, we identified Nmi (N-Myc and STATs Interactor) as a novel binding partner for Tip60 by a yeast two-hybrid screen. The association of Tip60 with Nmi was further confirmed by coimmunoprecipitation in mammalian cells. The zinc finger domain of Tip60 interacts with the NID repeats of Nmi, a region essential for the cytoplamic localization and homo- and heterodimerization of Nmi. We further showed that Nmi is an unstable protein and is targeted for proteasome-mediated degradation. The stability of Nmi can be enhanced by its association with Tip60, a process that is dependent on histone acetyltransferase activity of Tip60. The stabilization of Nmi by Tip60 is in part mediated by the translocation of Tip60 into cytoplasm to form distinct large cytoplasmic speckles. Our finding that Tip60 stabilizes Nmi through the formation of distinct cytoplasmic speckles provides a new mechanism to modulate Nmi-mediated functions.
authors.affiliation: Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, W353, Cleveland, OH 44106-4965, USA.
authors.forename: Keman
authors.initials: K
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D021381:Protein Transport; D020798:Two-Hybrid System Techniques
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C099927:NMI protein, human; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5