Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore-microtubule attachments

FEBS Lett. 2015 Nov 30;589(23):3588-94. doi: 10.1016/j.febslet.2015.10.017. Epub 2015 Oct 23.

Abstract

We previously reported that the spindle assembly checkpoint protein Bub3 is involved in regulating kinetochore-microtubule (KT-MT) attachments. Also, Bub3 was reported to interact with the microtubule motor protein dynein. Here we examined how this interaction contributes to KT-MT attachments. Depletion of Bub3 or dynein induced misaligned chromosomes, consistent with their role in KT-MT attachments. Unexpectedly, co-silencing of both proteins partially suppressed the misalignment phenotype and restored chromosome congression. Consistent with these observations, KT-MT attachments in co-depleted cells were stable, able to drive chromosome congression, and produce inter- and intra-kinetochore stretch, indicating they are functional. We suggest that a mutual antagonism exists between Bub3 and dynein to ensure optimal KT-MT attachments.

Keywords: Antagonistic interaction; Bub3; Chromosome congression; Dynein; Kinetochore–microtubule interaction; Spindly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / deficiency
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Chromosome Aberrations
  • Dyneins / antagonists & inhibitors*
  • Dyneins / deficiency
  • Dyneins / genetics*
  • Dyneins / metabolism
  • Gene Silencing*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Microtubules / metabolism*
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins

Substances

  • BUB3 protein, human
  • Cell Cycle Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Dyneins