title: Plk1-dependent phosphorylation of optineurin provides a negative feedback mechanism for mitotic progression.
abstract: Plk1 activation is required for progression through mitotic entry to cytokinesis. Here we show that at mitotic entry, Plk1 phosphorylates Optineurin (Optn) at serine 177 and that this dissociates Optn from the Golgi-localized GTPase Rab8, inducing its translocation into the nucleus. Mass spectrometry analysis revealed that Optn is associated with a myosin phosphatase complex (MP), which antagonizes the mitotic function of Plk1. Our data also indicate that Optn functionally connects this complex to Plk1 by promoting phosphorylation of the myosin phosphatase targeting subunit 1 (MYPT1). Accordingly, silencing Optn expression increases Plk1 activity and induces abscission failure and multinucleation, which were rescued upon expression of wild-type (WT) Optn, but not a phospho-deficient mutant (S177A) that cannot translocate into the nucleus during mitosis. Overall, these results highlight an important role of Optn in the spatial and temporal coordination of Plk1 activity.
authors.affiliation: Unité de Signalisation Moléculaire et Activation Cellulaire, Institut Pasteur, CNRS URA 2582, 75724 Paris Cedex 15, France.
authors.forename: David
authors.initials: D
authors.lastname: Kachaner
authors.forename: Josina
authors.initials: J
authors.lastname: Filipe
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Laplantine
authors.forename: Angela
authors.initials: A
authors.lastname: Bauch
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
authors.forename: Alain
authors.initials: A
authors.lastname: Israël
authors.forename: Robert
authors.initials: R
authors.lastname: Weil
mesh_terms: D021581:Active Transport, Cell Nucleus; D018797:Cell Cycle Proteins / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D025461:Feedback, Physiological; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D026901:Membrane Transport Proteins; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D035582:Transcription Factor TFIIIA / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D035582:Transcription Factor TFIIIA; D000097869:Polo-Like Kinase 1; C409460:OPTN protein, human