BubR1 kinase: protection against aneuploidy and premature aging

Trends Mol Med. 2015 Jun;21(6):364-72. doi: 10.1016/j.molmed.2015.04.003. Epub 2015 May 8.

Abstract

The multidomain protein kinase BubR1 is a central component of the mitotic spindle assembly checkpoint (SAC), an essential self-monitoring system of the eukaryotic cell cycle that ensures the high fidelity of chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bi-oriented on the mitotic spindle. We discuss the roles of BubR1 in the SAC and the implications of BubR1-mediated interactions that protect against aneuploidy. We also describe the emerging roles of BubR1 in cellular processes that extend beyond the SAC, discuss how mice models have revealed unanticipated functions for BubR1 in the regulation of normal aging, and the potential role of BubR1 as therapeutic target for the development of innovative anticancer therapies.

Keywords: BubR1; chromosome segregation; genome instability; kinetochore; premature aging; spindle assembly checkpoint (SAC).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging, Premature / enzymology*
  • Aging, Premature / genetics
  • Aging, Premature / metabolism
  • Aneuploidy*
  • Animals
  • Genomic Instability
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Models, Molecular
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • BUB1 protein, human
  • Protein Serine-Threonine Kinases