title: Ki67 antigen contributes to the timely accumulation of protein phosphatase 1γ on anaphase chromosomes.
abstract: Ki67 is a protein widely used as cell-proliferation marker, with its cellular functions being hardly unveiled. In this paper, we present the direct interaction between Ki67 and PP1γ, a protein phosphatase showing characteristic accumulation on anaphase chromosomes via the canonical PP1-binding motif within Ki67. In cells depleted of Ki67, PP1γ is targeted to anaphase chromosomes less efficiently. Additionally, overexpression of Ki67, but not a mutant form without the ability to bind PP1γ, induced ectopic localization of PP1γ οn metaphase chromosomes. These observations demonstrate that Ki67 is one factor that defines the cellular behavior of PP1γ in anaphase. To explore the specific roles of the subset of PP1γ recruited on chromosome via its interaction with Ki67 (PP1γ-Ki67), endogenous Ki67 was replaced with a Ki67 mutant deficient in its ability to interact with PP1γ. Although no obvious defects in the progression of mitosis were observed, the timing of dephosphorylation of the mutant Ki67 in anaphase was delayed, indicating that Ki67 itself is one of the substrates of PP1γ-Ki67.
authors.affiliation: Cellular Dynamics Laboratory, RIKEN, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: mtakagi@riken.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Cellular Dynamics Laboratory, RIKEN, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishiyama
authors.affiliation: Cellular Dynamics Laboratory, RIKEN, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Cellular Dynamics Laboratory, RIKEN, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: nimamoto@riken.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
mesh_terms: D000705:Anaphase / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation / Q000502:physiology; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; C517102:PPP1CC protein, human; D054645:Protein Phosphatase 1
keywords: Cell Biology; Chromosomes; Ki67; Mitosis; PP1γ; Phosphatase; Phosphoprotein Phosphatase 1 (PP1)