title: Mitotic regulation of SEPT9 protein by cyclin-dependent kinase 1 (Cdk1) and Pin1 protein is important for the completion of cytokinesis.
abstract: Precise cell division is essential for multicellular development, and defects in this process have been linked to cancer. Septins are a family of proteins that are required for mammalian cell division, but their function and mode of regulation during this process are poorly understood. Here, we demonstrate that cyclin-dependent kinase 1 (Cdk1) phosphorylates septin 9 (SEPT9) upon mitotic entry, and this phosphorylation controls association with the proline isomerase, Pin1. Both SEPT9 and Pin1 are critical for mediating the final separation of daughter cells. Expression of mutant SEPT9 that is defective in Pin1 binding was unable to rescue cytokinesis defects caused by SEPT9 depletion but rather induced dominant-negative defects in cytokinesis. However, unlike SEPT9 depletion, Pin1 was not required for the accumulation of the exocyst complex at the midbody. These results suggest that SEPT9 plays multiple roles in abscission, one of which is regulated by the action of Cdk1 and Pin1.
authors.affiliation: From the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada,; the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and.
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Estey
authors.affiliation: the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and.
authors.forename: Caterina
authors.initials: C
authors.lastname: Di Ciano-Oliveira
authors.affiliation: the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Froese
authors.affiliation: From the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada,; the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and.
authors.forename: Karen Y Y
authors.initials: KYY
authors.lastname: Fung
authors.affiliation: From the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada,; the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Steels
authors.affiliation: the Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
authors.affiliation: From the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada,; the Cell Biology Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, and. Electronic address: wtrimble@sickkids.ca.
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding; D058112:Septins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016203:CDC2 Protein Kinase; C474315:SEPTIN9 protein, human; D058112:Septins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: CDK (Cyclin-dependent Kinase); Cytokinesis; Cytoskeleton; GTPase; Phosphorylation; Pin1; Proline Isomerase; Septin