title: Plk1 phosphorylation of TRF1 is essential for its binding to telomeres.
abstract: In a search for Polo-like kinase 1 (Plk1) interaction proteins, we have identified TRF1 (telomeric repeat binding factor 1) as a potential Plk1 target. In this communication we report further characterization of the interaction. We show that Plk1 associates with TRF1, and Plk1 phosphorylates TRF1 at Ser-435 in vivo. Moreover, Cdk1, serving as a priming kinase, phosphorylates TRF1 to generate a docking site for Plk1 toward TRF1. In the presence of nocodazole, ectopic expression of wild type TRF1 but not TRF1 with alanine mutation in the Plk1 phosphorylation site induces apoptosis in cells containing short telomeres but not in cells containing long telomeres. Unexpectedly, down-regulation of TRF1 by RNA interference affects cell proliferation and results in obvious apoptosis in cells with short telomeres but not in cells with long telomeres. Importantly, we observe that telomeric DNA binding ability of TRF1 is cell cycle-regulated and reaches a peak during mitosis. Upon phosphorylation by Plk1 in vivo and in vitro, the ability of TRF1 to bind telomeric DNA is dramatically increased. These results demonstrate that Plk1 interacts with and phosphorylates TRF1 and suggest that Plk1-mediated phosphorylation is involved in both TRF1 overexpression-induced apoptosis and its telomeric DNA binding ability.
authors.affiliation: Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Zhao-Qiu
authors.initials: ZQ
authors.lastname: Wu
authors.affiliation: College of Chemistry, Sichuan University, Chengdu 610064, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Gregory
authors.initials: G
authors.lastname: Weber
authors.affiliation: Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, Indiana 47907. Electronic address: liu8@purdue.edu.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D016615:Telomere / Q000737:chemistry* / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D014162:Transfection; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D035321:Telomeric Repeat Binding Protein 1; D000097869:Polo-Like Kinase 1