The Cep192-organized aurora A-Plk1 cascade is essential for centrosome cycle and bipolar spindle assembly

Mol Cell. 2014 Aug 21;55(4):578-91. doi: 10.1016/j.molcel.2014.06.016. Epub 2014 Jul 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aurora Kinase A / metabolism
  • Cell Cycle Proteins / metabolism
  • Centrosome / physiology*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • HeLa Cells
  • Humans
  • Kinesin / metabolism
  • Mitosis / genetics
  • Mitosis / physiology
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / physiology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Proto-Oncogene Proteins
  • Xenopus Proteins
  • Aurora Kinase A
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Kinesin

Associated data

  • GENBANK/KJ567064