title: The Cep192-organized aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly.
abstract: As cells enter mitosis, the two centrosomes separate and grow dramatically, each forming a nascent spindle pole that nucleates a radial array of microtubules. Centrosome growth (and associated microtubule nucleation surge), termed maturation, involves the recruitment of pericentriolar material components via an as-yet unknown mechanism. Here, we show that Cep192 binds Aurora A and Plk1, targets them to centrosomes in a pericentrin-dependent manner, and promotes sequential activation of both kinases via T-loop phosphorylation. The Cep192-bound Plk1 then phosphorylates Cep192 at several residues to generate the attachment sites for the γ-tubulin ring complex and, possibly, other pericentriolar material components, thus promoting their recruitment and subsequent microtubule nucleation. We further found that the Cep192-dependent Aurora A-Plk1 activity is essential for kinesin-5-mediated centrosome separation, bipolar spindle formation, and equal centrosome/centriole segregation into daughter cells. Thus, our study identifies a Cep192-organized signaling cascade that underlies both centrosome maturation and bipolar spindle assembly.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. Electronic address: vladimir_joukov@hms.harvard.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Joukov
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Walter
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Arcangela
authors.initials: A
authors.lastname: De Nicolo
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D018385:Centrosome / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D008941:Spindle Apparatus / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064096:Aurora Kinase A; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D029867:Xenopus Proteins; D000097869:Polo-Like Kinase 1