Article: article from journal or magazin.
A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells.
Faithful cell-cycle progression is tightly controlled by the ubiquitin-proteasome system. Here we identify a human Cullin 3-based E3 ligase (Cul3) which is essential for mitotic division. In a complex with the substrate-specific adaptors KLHL9 and KLHL13, Cul3 is required for correct chromosome alignment in metaphase, proper midzone and midbody formation, and completion of cytokinesis. This Cul3-based E3 ligase removes components of the chromosomal passenger complex from mitotic chromosomes and allows their accumulation on the central spindle during anaphase. Aurora B directly binds to the substrate-recognition domain of KLHL9 and KLHL13 in vitro, and coimmunoprecipitates with the Cul3 complex during mitosis. Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo, and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro. We thus propose that the Cul3/KLHL9/KLHL13 E3 ligase controls the dynamic behavior of Aurora B on mitotic chromosomes, and thereby coordinates faithful mitotic progression and completion of cytokinesis.
Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, Chromosomes, Human, Cullin Proteins/genetics, Cullin Proteins/metabolism, Cytokinesis, Hela Cells, Humans, Mitosis, Mitotic Spindle Apparatus, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/metabolism, Ubiquitin/metabolism, Ubiquitin-Protein Ligase Complexes/genetics, Ubiquitin-Protein Ligase Complexes/metabolism, Ubiquitin-Protein Ligases/genetics, Ubiquitin-Protein Ligases/metabolism
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