title: Multiple protein phosphatases are required for mitosis in Drosophila.
abstract: BACKGROUND
  Approximately one-third of the Drosophila kinome has been ascribed some cell-cycle function. However, little is known about which of its 117 protein phosphatases (PPs) or subunits have counteracting roles.
  
  
  RESULTS
  We investigated mitotic roles of PPs through systematic RNAi. We found that G(2)-M progression requires Puckered, the JNK MAP-kinase inhibitory phosphatase and PP2C in addition to string (Cdc25). Strong mitotic arrest and chromosome congression failure occurred after Pp1-87B downregulation. Chromosome alignment and segregation defects also occurred after knockdown of PP1-Flapwing, not previously thought to have a mitotic role. Reduction of several nonreceptor tyrosine phosphatases produced spindle and chromosome behavior defects, and for corkscrew, premature chromatid separation. RNAi of the dual-specificity phosphatase, Myotubularin, or the related Sbf "antiphosphatase" resulted in aberrant mitotic chromosome behavior. Finally, for PP2A, knockdown of the catalytic or A subunits led to bipolar monoastral spindles, knockdown of the Twins B subunit led to bridged and lagging chromosomes, and knockdown of the B' Widerborst subunit led to scattering of all mitotic chromosomes. Widerborst was associated with MEI-S332 (Shugoshin) and required for its kinetochore localization.
  
  
  CONCLUSIONS
  We identify cell-cycle roles for 22 of 117 Drosophila PPs. Involvement of several PPs in G(2) suggests multiple points for its regulation. Major mitotic roles are played by PP1 with tyrosine PPs and Myotubularin-related PPs having significant roles in regulating chromosome behavior. Finally, depending upon its regulatory subunits, PP2A regulates spindle bipolarity, kinetochore function, and progression into anaphase. Discovery of several novel cell-cycle PPs identifies a need for further studies of protein dephosphorylation.
authors.affiliation: Cancer Research United Kingdom, Cell Cycle Genetics Research Group, Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, United Kingdom. fc273@cam.ac.uk
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Vincent
authors.initials: V
authors.lastname: Archambault
authors.forename: Ashok
authors.initials: A
authors.lastname: Kar
authors.forename: Pietro
authors.initials: P
authors.lastname: Lio'
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: D'Avino
authors.forename: Rita
authors.initials: R
authors.lastname: Sinka
authors.forename: Kathryn
authors.initials: K
authors.lastname: Lilley
authors.forename: Ernest D
authors.initials: ED
authors.lastname: Laue
authors.forename: Peter
authors.initials: P
authors.lastname: Deak
authors.forename: Luisa
authors.initials: L
authors.lastname: Capalbo
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004330:Drosophila / Q000201:enzymology* / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D029721:Drosophila Proteins; C576742:Sbf protein, Drosophila; D010749:Phosphoprotein Phosphatases