Xenopus Shugoshin 2 regulates the spindle assembly pathway mediated by the chromosomal passenger complex

EMBO J. 2012 Mar 21;31(6):1467-79. doi: 10.1038/emboj.2012.4. Epub 2012 Jan 24.

Abstract

Shugoshins (Sgo) are conserved proteins that act as protectors of centromeric cohesion and as sensors of tension for the machinery that eliminates improper kinetochore-microtubule attachments. Most vertebrates contain two Sgo proteins, but their specific functions are not always clear. Xenopus laevis Sgo1, XSgo1, protects centromeric cohesin from the prophase dissociation pathway. Here, we report the identification of XSgo2 and show that it does not regulate cohesion. Instead, we find that it participates in bipolar spindle assembly. Both Sgo proteins interact physically with the Chromosomal Passenger Complex (CPC) containing Aurora B, a key regulator of mitosis, but the functional consequences of such interaction are distinct. XSgo1 is required for proper localization of the CPC while XSgo2 positively contributes to its activation and the subsequent phosphorylation of at least one key substrate for bipolar spindle assembly, the microtubule depolymerizing kinesin MCAK (Mitotic Centromere-Associated Kinesin). Thus, the two Xenopus Sgo proteins have non-overlapping functions in chromosome segregation. Our results further suggest that this functional specificity could rely on the association of XSgo1 and XSgo2 with different regulatory subunits of the PP2A complex.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinases
  • Cell Cycle Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation*
  • Chromosomes
  • Kinesins / genetics
  • Kinesins / metabolism
  • Microtubules / genetics
  • Microtubules / metabolism
  • Mitosis / genetics
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Spindle Apparatus / genetics*
  • Spindle Apparatus / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / genetics*
  • Xenopus laevis / metabolism*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • Sgo protein, Xenopus
  • Xenopus Proteins
  • cohesins
  • mitotic centromere-associated kinesin, Xenopus
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • haspin protein, Xenopus laevis
  • Protein Phosphatase 2
  • Kinesins

Associated data

  • GENBANK/JQ412129