title: Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators.
abstract: Reversible phosphorylation is a fundamental regulatory mechanism, intricately coordinated by kinases and phosphatases, two classes of enzymes widely disrupted in human disease. To better understand the functions of the relatively understudied phosphatases, we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains. We identified 1,335 high-confidence interactions (1,104 previously unreported), implicating these phosphatases in the regulation of a variety of cellular processes. Systematic phenotypic profiling of phosphatase catalytic and regulatory subunits revealed that phosphatases from every evolutionary family impinge on mitosis. Using clues from the interactome, we have uncovered unsuspected roles for DUSP19 in mitotic exit, CDC14A in regulating microtubule integrity, PTPRF in mitotic retraction fiber integrity, and DUSP23 in centriole duplication. The functional phosphatase interactome further provides a rich resource for ascribing functions for this important class of enzymes.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: St-Denis
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Gagan D
authors.initials: GD
authors.lastname: Gupta
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Zhen Yuan
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gonzalez-Badillo
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Amanda O
authors.initials: AO
authors.lastname: Veri
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: James D R
authors.initials: JDR
authors.lastname: Knight
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Dushyandi
authors.initials: D
authors.lastname: Rajendran
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Couzens
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Ko W
authors.initials: KW
authors.lastname: Currie
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Johnny M
authors.initials: JM
authors.lastname: Tkach
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Sally W T
authors.initials: SWT
authors.lastname: Cheung
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: pelletier@lunenfeld.ca.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: gingras@lunenfeld.ca.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
mesh_terms: D005075:Biological Evolution; D002502:Centrioles / Q000378:metabolism; D054637:Dual-Specificity Phosphatases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D021122:Protein Subunits; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; C497817:DUSP23 protein, human; D054637:Dual-Specificity Phosphatases; C516772:PTPRF protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: CDC14A; DUSP19; DUSP23; PLK4; PTPRF; interactome; mitosis; phosphatase; phosphorylation; proteomics