title: Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation.
abstract: Telomere length is critical for chromosome stability that affects cell proliferation and survival. Telomere elongation by telomerase is inhibited by the telomeric protein, TRF1. Tankyrase-1 (TNKS1) poly(ADP-ribosyl)ates TRF1 and releases TRF1 from telomeres, thereby allowing access of telomerase to the telomeres. TNKS1-mediated poly(ADP-ribosyl)ation also appears to be crucial for regulating the mitotic cell cycle. In searching for proteins that interact with polo-like kinase-1 (Plk1) by using complex proteomics, we identified TNKS1 as a novel Plk1-binding protein. Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. Taken together, our results provide evidence of a novel molecular mechanism in which phosphorylation of TNKS1 by Plk1 may help regulate mitotic spindle assembly and promote telomeric chromatin maintenance.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
authors.forename: G-H
authors.initials: GH
authors.lastname: Ha
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Go
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Seimiya
authors.forename: D H
authors.initials: DH
authors.lastname: Chung
authors.forename: C-W
authors.initials: CW
authors.lastname: Lee
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004795:Enzyme Stability; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D038501:Tankyrases / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology*; D000097869:Polo-Like Kinase 1
chemical_list: D000246:Adenosine Diphosphate Ribose; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D038501:Tankyrases; D000097869:Polo-Like Kinase 1; C418109:TNKS protein, human