The SUMO protease SENP6 is essential for inner kinetochore assembly

J Cell Biol. 2010 Mar 8;188(5):681-92. doi: 10.1083/jcb.200909008.

Abstract

We have analyzed the mitotic function of SENP6, a small ubiquitin-like modifier (SUMO) protease that disassembles conjugated SUMO-2/3 chains. Cells lacking SENP6 showed defects in spindle assembly and metaphase chromosome congression. Analysis of kinetochore composition in these cells revealed that a subset of proteins became undetectable on inner kinetochores after SENP6 depletion, particularly the CENP-H/I/K complex, whereas other changes in kinetochore composition mimicked defects previously reported to result from CENP-H/I/K depletion. We further found that CENP-I is degraded through the action of RNF4, a ubiquitin ligase which targets polysumoylated proteins for proteasomal degradation, and that SENP6 stabilizes CENP-I by antagonizing RNF4. Together, these findings reveal a novel mechanism whereby the finely balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Aurora Kinases
  • Chromosomes / metabolism
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / ultrastructure
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spindle Apparatus / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNF4 protein, human
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Cysteine Endopeptidases
  • SENP6 protein, human