title: RanGTP aids anaphase entry through Ubr5-mediated protein turnover.
abstract: 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.
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Di
authors.initials: D
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China zheng@ciwemb.edu xlzhu@sibcb.ac.cn.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 zheng@ciwemb.edu xlzhu@sibcb.ac.cn.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000705:Anaphase; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D006224:Cricetinae; D020868:Gene Silencing; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D059748:Proteolysis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000502:physiology*
chemical_list: C489444:BUB3 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C120587:RAN protein, human; C587673:ZNF207 protein, human; D028961:beta Karyopherins; D006160:Guanosine Triphosphate; C117617:UBR5 protein, human; D044767:Ubiquitin-Protein Ligases; D020931:ran GTP-Binding Protein