Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora

Chromosoma. 2008 Oct;117(5):457-69. doi: 10.1007/s00412-008-0165-5. Epub 2008 Jun 3.

Abstract

Polo-like kinase 1 (Plk1) and Aurora A play key roles in centrosome maturation, spindle assembly, and chromosome segregation during cell division. Here we show that the functions of these kinases during early mitosis are coordinated through Bora, a partner of Aurora A first identified in Drosophila. Depletion of human Bora (hBora) results in spindle defects, accompanied by increased spindle recruitment of Aurora A and its partner TPX2. Conversely, hBora overexpression induces mislocalization of Aurora A and monopolar spindle formation, reminiscent of the phenotype seen in Plk1-depleted cells. Indeed, Plk1 regulates hBora. Following Cdk1-dependent recruitment, Plk1 triggers hBora destruction by phosphorylating a recognition site for SCF(Beta-TrCP). Plk1 depletion or inhibition results in a massive accumulation of hBora, concomitant with displacement of Aurora A from spindle poles and impaired centrosome maturation, but remarkably, co-depletion of hBora partially restores Aurora A localization and bipolar spindle formation. This suggests that Plk1 controls Aurora A localization and function by regulating cellular levels of hBora.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Cell Cycle Proteins / drug effects
  • Cell Cycle Proteins / metabolism*
  • Centrosome / physiology
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Mice
  • Mitosis / physiology
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Spindle Apparatus / physiology
  • beta-Transducin Repeat-Containing Proteins / genetics
  • beta-Transducin Repeat-Containing Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • beta-Transducin Repeat-Containing Proteins
  • bora protein, human
  • SKP Cullin F-Box Protein Ligases
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1