title: Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome amplification.
abstract: The presence of more than 2 centrosomes (centrosome amplification) leads to defective mitosis and chromosome segregation errors, is frequently found in a variety of cancer types, and believed to be the major cause of chromosome instability. One mechanism for generation of amplified centrosomes is over-duplication of centrosomes in a single cell cycle, which is expected to occur when cells are temporarily arrested. There are a growing number of kinases that are critical for induction and promotion of centrosome amplification in the cell cycle-arrested cells, including Rho-associated kinase (ROCK2), Polo-like kinase 2 (PLK2) and PLK4. Here, we tested whether these kinases induce centrosome amplification in a linear pathway or parallel pathways. We first confirmed that ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the cells arrested by exposure to DNA synthesis inhibitor. Using the centrosome amplification rescue assay, we found that PLK2 indirectly activates ROCK2 via phosphorylating nucleophosmin (NPM), and PLK4 functions downstream of ROCK2 to drive centrosome amplification in the arrested cells.
authors.affiliation: a Department of Molecular Oncology ; H. Lee Moffitt Cancer Center & Research Institute ; Tampa , FL USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Ling
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hanashiro
authors.forename: Tran H
authors.initials: TH
authors.lastname: Luong
authors.forename: Luis
authors.initials: L
authors.lastname: Benavides
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukasawa
mesh_terms: D018385:Centrosome / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D055786:Gene Knockout Techniques; D015151:Immunoblotting; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; C490219:PLK4 protein, human; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases
keywords: Aph, aphidicolin; B23; CDK2, Cyclin-dependent kinase 2; DN, dominant-negative; KD, kinase-dead; MEFs, mouse embryonic fibroblasts; NPM; NPM, Nucleophosmin; PLK2; PLK2, Polo-like kinase 2; PLK4; PLK4, Polo-like kinase 4; Puro, puromycin; ROCK2; ROCK2, Rho-(associated) kinase; centrosome; nucleophosmin; polo-like kinase; wt, wild type