RSK2 is a kinetochore-associated protein that participates in the spindle assembly checkpoint

Oncogene. 2010 Jun 17;29(24):3566-74. doi: 10.1038/onc.2010.105. Epub 2010 Apr 12.

Abstract

The spindle assembly checkpoint (SAC) prevents anaphase onset until all the chromosomes have successfully attached to the spindle microtubules. The MAP kinase (MAPK) is an important player in this pathway, however its exact role is not fully understood. One major target of MAPK is the p90 ribosomal protein S6 kinase (RSKs) family. In this study, we analyse whether Rsk2 could participate in the activation of the SAC. Our data indicate that this protein is localized at the kinetochores under checkpoint conditions. Moreover, it is essential for the SAC activity in Xenopus egg extracts as its depletion prevents metaphase arrest as well as the kinetochore localization of the other SAC components. We also show that this kinase might also participate in the maintenance of the SAC in mammalian cells as Rsk2 knockdown in these cells prevents the kinetochore localization of Mad1, Mad2 and CENP-E under checkpoint conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Cycle*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Mad2 Proteins
  • Metaphase
  • Nuclear Proteins / metabolism
  • Plasmids / genetics
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Repressor Proteins / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa / deficiency
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Spindle Apparatus / metabolism*
  • Tissue Extracts / metabolism
  • Xenopus

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • MAD1L1 protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Tissue Extracts
  • centromere protein E
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3