title: Mitotic phosphorylation of tankyrase, a PARP that promotes spindle assembly, by GSK3.
abstract: The assembly and function of mitotic spindles require poly(ADP-ribosyl)ation of spindle components by tankyrase, a poly(ADP-ribose) polymerase that aggregates to spindle poles during mitosis. Tankyrase itself is phosphorylated during mitosis, but the kinases involved remain undefined. Herein we report that mitotic phosphorylation of tankyrase is abrogated in cells treated with the GSK3 inhibitors LiCl and indirubin. Moreover, the electrophoretic mobility-shift of tankyrase arising from mitotic phosphorylation can be reproduced in vitro by GSK3-mediated phosphorylation. Lastly, mutagenesis study suggested that GSK3 in vitro phosphorylates tankyrase on S978, T982, S987, and S991, residues that comprise two adjacent copies of the canonical GSK3 phospho-acceptor motif [S/T]-X-X-X-[S/T]. Collectively, our data suggest that GSK3 contributes to mitotic tankyrase phosphorylation, raising the possibility that this phosphorylation might mediate some of the established roles of GSK3 in spindle assembly and mitotic progression.
authors.affiliation: Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, CA 92093-0673, USA.
authors.forename: Tsung-Yin J
authors.initials: TY
authors.lastname: Yeh
authors.forename: Juan I
authors.initials: JI
authors.lastname: Sbodio
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Chi
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology* / Q000648:ultrastructure*; D038501:Tankyrases / Q000378:metabolism*
chemical_list: C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; C498822:Tnks protein, mouse; D038362:Glycogen Synthase Kinase 3