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PMID:20212317

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Citation

Mukhopadhyay, D, Arnaoutov, A and Dasso, M (2010) The SUMO protease SENP6 is essential for inner kinetochore assembly. J. Cell Biol. 188:681-92

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.

Links

PubMed PMC2835930 Online version:10.1083/jcb.200909008

Keywords

Animals; 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; Mitotic Spindle Apparatus/metabolism; 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; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:RNF4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92674

F

Seeded From UniProt

complete

HUMAN:CENPI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P78317

F

Seeded From UniProt

complete

HUMAN:CENPI

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9GZR1

F

Seeded From UniProt

complete

HUMAN:CENPI

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SENP6

involved_in

GO:0070646: protein modification by small protein removal

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SENP6

involved_in

GO:0090169: regulation of spindle assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SENP6

involved_in

GO:0090234: regulation of kinetochore assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SENP6

involved_in

GO:0016926: protein desumoylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SENP6

enables

GO:0070139: SUMO-specific endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SENP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92674

F

Seeded From UniProt

complete

HUMAN:CENPH

located_in

GO:0000776: kinetochore

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RNF4

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNF4

involved_in

GO:0090169: regulation of spindle assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RNF4

involved_in

GO:0090234: regulation of kinetochore assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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