Fission yeast homologues of the B′ subunit of protein phosphatase 2A: Multiple roles in mitotic cell division and functional interaction with calcineurin

Osamu Tanabe, Dai Hirata, Hirofumi Usui, Yasumasa Nishito, Tokichi Miyakawa, Kazuhiko Igarashi, Masao Takeda

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background: Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase distributed in eukaryotes from yeast to human, and plays pivotal roles in diverse cellular functions such as metabolism, cell cycle progression, gene expression and development. PP2A holoenzyme is a heterodimer of a catalytic subunit C and a regulatory subunit A, or a heterotrimer of C, A and a variable regulatory subunit consisting of three families; B, B′, and PR72. Specific functions for each variable subunit are not well understood. Results: Two fission yeast genes pbp1+ and pbp2+ homologous to the regulatory subunit B′ were isolated. Physical in vivo interaction of the gene products with the catalytic subunit was demonstrated. A double disruption haploid mutant (Δpbp1Δpbp2) showed growth defect, cell shape and size abnormality, multiseptation and anucleated cell formation due to abnormality in septum positioning. These phenotypes were suppressed by human B′ cDNA, indicating the striking conservation of the B′ function from yeast to human. Over-expression of fission yeast B′ led to growth defects, a loss of cell shape polarity, septal abnormality and anucleated cell formation. Δpbp1Δpbp2 and pbp1 null haploids were hypersensitive to calcineurin inhibitors, cyclosporin A and FK506, with which the mutants underwent arrest at post-anaphase and cell lysis. Double disruption of calcineurin and pbp1+, but not pbp2+, genes led to synthetic lethality. Conclusion: The fission yeast B′ subunit of PP2A plays critical roles in cell shape control and septum formation, and shares essential functions with calcineurin for viability, possibly through their roles in cytokinesis and cell wall integrity.

Original languageEnglish
Pages (from-to)455-473
Number of pages19
JournalGenes to Cells
Volume6
Issue number5
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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