title: Regulation of NDR1 activity by PLK1 ensures proper spindle orientation in mitosis.
abstract: Accurate chromosome segregation during mitosis requires the physical separation of sister chromatids which depends on correct position of mitotic spindle relative to membrane cortex. Although recent work has identified the role of PLK1 in spindle orientation, the mechanisms underlying PLK1 signaling in spindle positioning and orientation have not been fully illustrated. Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. Importantly, persistent expression of non-phosphorylatable NDR1 mutant perturbs spindle orientation. Mechanistically, PLK1-mediated phosphorylation protects the binding of Mob1 to NDR1 and subsequent NDR1 activation. These findings define a conserved signaling axis that integrates dynamic kinetochore-microtubule interaction and spindle orientation control to genomic stability maintenance.
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Shanghai Institute of Biochemistry and Cell Biology, Shanghai 200031, China.
authors.forename: Maomao
authors.initials: M
authors.lastname: Yan
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China.
authors.forename: Lingluo
authors.initials: L
authors.lastname: Chu
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Molecular Imaging Center, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Molecular Imaging Center, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Molecular Imaging Center, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
authors.forename: Guanglan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Gomez
authors.affiliation: UCL Cancer Institute, University College London, London WC1E 6BT, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hergovich
authors.affiliation: Shanghai Institute of Biochemistry and Cell Biology, Shanghai 200031, China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China.
authors.forename: Xinjiao
authors.initials: X
authors.lastname: Gao
authors.affiliation: 1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Molecular Imaging Center, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D008941:Spindle Apparatus; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C491614:STK38 protein, human