title: SHCBP1 is required for midbody organization and cytokinesis completion.
abstract: The centralspindlin complex, which is composed of MKLP1 and MgcRacGAP, is one of the crucial factors involved in cytokinesis initiation. Centralspindlin is localized at the middle of the central spindle during anaphase and then concentrates at the midbody to control abscission. A number of proteins that associate with centralspindlin have been identified. These associating factors regulate furrowing and abscission in coordination with centralspindlin. A recent study identified a novel centralspindlin partner, called Nessun Dorma, which is essential for germ cell cytokinesis in Drosophila melanogaster. SHCBP1 is a human ortholog of Nessun Dorma that associates with human centralspindlin. In this report, we analyzed the interaction of SHCBP1 with centralspindlin in detail and determined the regions that are required for the interaction. In addition, we demonstrate that the central region is necessary for the SHCBP1 dimerization. Both MgcRacGAP and MKLP1 are degraded once cells exit mitosis. Similarly, endogenous and exogenous SHCBP1 were degraded with mitosis progression. Interestingly, SHCBP1 expression was significantly reduced in the absence of centralspindlin, whereas centralspindlin expression was not affected by SHCBP1 knockdown. Finally, we demonstrate that SHCBP1 depletion promotes midbody structure disruption and inhibits abscission, a final stage of cytokinesis. Our study gives novel insight into the role of SHCBP in cytokinesis completion.
authors.affiliation: a Division of Cancer Biology ; Nagoya University Graduate School of Medicine ; Nagoya , Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Asano
authors.forename: Hitoki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hyodo
authors.forename: Satoko
authors.initials: S
authors.lastname: Ito
authors.forename: Masao
authors.initials: M
authors.lastname: Maeda
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Michinari
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
mesh_terms: D048749:Cytokinesis; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C000599466:SHCBP1 protein, human; D055765:Shc Signaling Adaptor Proteins
keywords: ECT2, epithelial cell transforming sequence 2 oncogene; MKLP1; MKLP1, mitotic kinesin-like protein 1; MgcRacGAP; MgcRacGAP, male germ cell Rac GTPase-activating protein; PLK1, polo-like kinase 1; PbH1, parallel b-helix repeats; SHCBP1; SHCBP1, SHC SH2-domain binding protein 1; abscission; centralspindlin; cytokinesis; midbody