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PMID: 20212317 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

The SUMO protease SENP6 is essential for inner kinetochore assembly.

The Journal of cell biology ·Vol. 188 ·No. 5 ·2010-03-08 ·Pages 681-92

Mukhopadhyay D, Arnaoutov A, Dasso M

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.

MeSH Terms
Animals Aurora Kinases Chromosomes/metabolism Cysteine Endopeptidases/genetics,metabolism DNA-Binding Proteins/genetics,metabolism HeLa Cells Histones/genetics,metabolism Humans Kinetochores/metabolism,ultrastructure Microtubules/metabolism Mitosis/physiology Multiprotein Complexes/metabolism Nuclear Proteins/genetics,metabolism Protein Serine-Threonine Kinases/metabolism RNA, Small Interfering/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Spindle Apparatus/metabolism Transcription Factors/genetics,metabolism
Chemicals
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mukhopadhyay Debaditya
Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Arnaoutov Alexei
Dasso Mary
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200909008
Published
2010-03-08
Pages
681-92
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2835930
Subset
IM
Grants
Intramural NIH HHS · Z01 HD001902 · United States
Intramural NIH HHS · Z01 HD008740 · United States
External Links
PubMed source DOI: 10.1083/jcb.200909008 PMC Full Text View journal details
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