Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1

Cell Cycle. 2007 Jul 1;6(13):1579-85. doi: 10.4161/cc.6.13.4442. Epub 2007 May 16.

Abstract

Physical connection between the sister chromatids is mediated by the cohesin protein complex. During prophase, cohesin is removed from the chromosome arms while the centromeres remain united. Shugoshin1 (Sgo1) is required for maintenance of centromeric cohesion from prophase to the metaphase-anaphase transition. Furthermore, Sgo1 has been proposed to regulate kinetochore microtubule stability and sense interkinetochore tension, two tasks which are tightly coupled with the function of the Chromosomal Passenger Complex (CPC) and Polo-like kinase 1 (Plk1). Here we show that depletion or chemical inhibition of Aurora B kinase (AurB), the catalytic subunit of the CPC, disrupts accumulation of Sgo1 on the kinetochores in HeLa cells and causes Sgo1 to localize on the chromosome arms. RNAi assays show that depletion of Sgo1 did not affect AurB localization but diminished Plk1 kinetochore binding. Furthermore, we demonstrate that vertebrate Sgo1 is phosphorylated by both AurB and Plk1 in vitro. The data presented here includes an extensive analysis of kinetochore targeting interdependencies of mitotic proteins that propose a novel branch in kinetochore assembly where Sgo1 and Plk1 have central roles. Furthermore our studies implicate Sgo1 in the tension sensing mechanism of the spindle checkpoint by regulating Plk1 kinetochore affinity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology*
  • Chromosomal Proteins, Non-Histone / metabolism
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Microfilament Proteins / metabolism
  • Models, Biological
  • Phosphorylation
  • Protein Kinases / physiology
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • Proto-Oncogene Proteins
  • SGO1 protein, human
  • centromere protein F
  • Protein Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1