The SUMO protease SENP6 is essential for inner kinetochore assembly.
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.
Mukhopadhyay
Debaditya
D
Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Arnaoutov
Alexei
A
Dasso
Mary
M
D000818:Animals; D064127:Aurora Kinases; D002875:Chromosomes / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C114070:RNF4 protein, human; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human