title: ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation.
abstract: Proper dynamic regulation of the spindle is essential for successful cell division. However, the molecular mechanisms that regulate spindle dynamics in mitosis are not fully understood. In this study, we show that Cullin 5-interacting suppressor of cytokine signaling box protein ASB7 ubiquitinates DDA3, a regulator of spindle dynamics, thereby targeting it for proteasomal degradation. The presence of microtubules (MTs) prevented the ASB7-DDA3 interaction, thus stabilizing DDA3. Knockdown of ASB7 decreased MT polymerization and increased the proportion of cells with unaligned chromosomes, and this phenotype was rescued by deletion of DDA3. Collectively, these data indicate that ASB7 plays a crucial role in regulating spindle dynamics and genome integrity by controlling the expression of DDA3.
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Uematsu
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan okumura.fumihiko@a.mbox.nagoya-u.ac.jp z47617a@nucc.cc.nagoya-u.ac.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okumura
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan.
authors.forename: Syunsuke
authors.initials: S
authors.lastname: Tonogai
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Joo-Okumura
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan.
authors.forename: Dawit Hailu
authors.initials: DH
authors.lastname: Alemayehu
authors.affiliation: Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akihiko
authors.identifier: http://orcid.org/0000-0001-9497-7557
authors.initials: A
authors.lastname: Nishikimi
authors.affiliation: Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan Research Center for Advanced Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshinori
authors.identifier: http://orcid.org/0000-0003-2335-8745
authors.initials: Y
authors.lastname: Fukui
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakatsukasa
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Aichi 464-8602, Japan okumura.fumihiko@a.mbox.nagoya-u.ac.jp z47617a@nucc.cc.nagoya-u.ac.jp.
authors.forename: Takumi
authors.identifier: http://orcid.org/0000-0001-8541-447X
authors.initials: T
authors.lastname: Kamura
mesh_terms: D017487:Ankyrins / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D044842:Cullin Proteins / Q000378:metabolism; D015894:Genome, Human; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D008941:Spindle Apparatus / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C000619642:ASB7 protein, human; D017487:Ankyrins; C496871:CUL5 protein, human; D044842:Cullin Proteins; C485740:PSRC1 protein, human; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex