RanGTP aids anaphase entry through Ubr5-mediated protein turnover.
RanGTP is known to regulate the spindle assembly checkpoint (SAC), but the underlying molecular mechanism is unclear. BuGZ stabilizes SAC protein Bub3 through direct interaction and facilitates its mitotic function. Here we show that RanGTP promotes the turnover of BuGZ and Bub3 in metaphase, which in turn facilitates metaphase-to-anaphase transition. ... BuGZ and Bub3 interact with either importin-β or an E3 ubiquitin ligase, Ubr5. RanGTP promotes the dissociation of importin-β from BuGZ and Bub3 in metaphase. This results in increased binding of BuGZ and Bub3 to Ubr5, leading to ubiquitination and subsequent turnover of both proteins. We propose that elevated metaphase RanGTP levels use Ubr5 to couple overall chromosome congression to SAC silencing.
Mesh Terms:
Anaphase, Animals, Cell Cycle Proteins, Cricetinae, Gene Silencing, Guanosine Triphosphate, HeLa Cells, Humans, M Phase Cell Cycle Checkpoints, Microtubule-Associated Proteins, Proteolysis, Ubiquitin-Protein Ligases, Ubiquitination, beta Karyopherins, ran GTP-Binding Protein
Anaphase, Animals, Cell Cycle Proteins, Cricetinae, Gene Silencing, Guanosine Triphosphate, HeLa Cells, Humans, M Phase Cell Cycle Checkpoints, Microtubule-Associated Proteins, Proteolysis, Ubiquitin-Protein Ligases, Ubiquitination, beta Karyopherins, ran GTP-Binding Protein
J. Cell Biol.
Date: Oct. 12, 2015
PubMed ID: 26438829
View in: Pubmed Google Scholar
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