Multiple Protein Phosphatases Are Required for Mitosis in Drosophila

Feng Chen, Vincent Archambault, Ashok Kar, Pietro Lio', Pier Paolo D'Avino, Rita Sinka, Kathryn Lilley, Ernest D. Laue, P. Deák, Luisa Capalbo, David M. Glover

Research output: Contribution to journalArticle

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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 G2-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 G2 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.

Original languageEnglish
Pages (from-to)293-303
Number of pages11
JournalCurrent Biology
Volume17
Issue number4
DOIs
Publication statusPublished - Feb 20 2007

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Phosphoprotein Phosphatases
Chromosomes
Mitosis
mitosis
Drosophila
chromosomes
Kinetochores
proteins
cell cycle
kinetochores
RNA Interference
Phosphoric Monoester Hydrolases
mitogen-activated protein kinase
Cell Cycle
Dual-Specificity Phosphatases
MAP Kinase Kinase 4
Chromosomes, Human, 4-5
Drosophila Proteins
Cells
Cell Cycle Proteins

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Chen, F., Archambault, V., Kar, A., Lio', P., D'Avino, P. P., Sinka, R., ... Glover, D. M. (2007). Multiple Protein Phosphatases Are Required for Mitosis in Drosophila. Current Biology, 17(4), 293-303. https://doi.org/10.1016/j.cub.2007.01.068

Multiple Protein Phosphatases Are Required for Mitosis in Drosophila. / Chen, Feng; Archambault, Vincent; Kar, Ashok; Lio', Pietro; D'Avino, Pier Paolo; Sinka, Rita; Lilley, Kathryn; Laue, Ernest D.; Deák, P.; Capalbo, Luisa; Glover, David M.

In: Current Biology, Vol. 17, No. 4, 20.02.2007, p. 293-303.

Research output: Contribution to journalArticle

Chen, F, Archambault, V, Kar, A, Lio', P, D'Avino, PP, Sinka, R, Lilley, K, Laue, ED, Deák, P, Capalbo, L & Glover, DM 2007, 'Multiple Protein Phosphatases Are Required for Mitosis in Drosophila', Current Biology, vol. 17, no. 4, pp. 293-303. https://doi.org/10.1016/j.cub.2007.01.068
Chen F, Archambault V, Kar A, Lio' P, D'Avino PP, Sinka R et al. Multiple Protein Phosphatases Are Required for Mitosis in Drosophila. Current Biology. 2007 Feb 20;17(4):293-303. https://doi.org/10.1016/j.cub.2007.01.068
Chen, Feng ; Archambault, Vincent ; Kar, Ashok ; Lio', Pietro ; D'Avino, Pier Paolo ; Sinka, Rita ; Lilley, Kathryn ; Laue, Ernest D. ; Deák, P. ; Capalbo, Luisa ; Glover, David M. / Multiple Protein Phosphatases Are Required for Mitosis in Drosophila. In: Current Biology. 2007 ; Vol. 17, No. 4. pp. 293-303.
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