The diverging role of CDC14B: from mitotic exit in yeast to cell fate control in humans

EMBO J. 2023 Aug 15;42(16):e114364. doi: 10.15252/embj.2023114364. Epub 2023 Jul 26.

Abstract

CDC14, originally identified as crucial mediator of mitotic exit in budding yeast, belongs to the family of dual-specificity phosphatases (DUSPs) that are present in most eukaryotes. Contradicting data have sparked a contentious discussion whether a cell cycle role is conserved in the human paralogs CDC14A and CDC14B but possibly masked due to redundancy. Subsequent studies on CDC14A and CDC14B double knockouts in human and mouse demonstrated that CDC14 activity is dispensable for mitotic progression in higher eukaryotes and instead suggested functional specialization. In this review, we provide a comprehensive overview of our current understanding of how faithful cell division is linked to phosphorylation and dephosphorylation and compare functional similarities and divergences between the mitotic phosphatases CDC14, PP2A, and PP1 from yeast and higher eukaryotes. Furthermore, we review the latest discoveries on CDC14B, which identify this nuclear phosphatase as a key regulator of gene expression and reveal its role in neuronal development. Finally, we discuss CDC14B functions in meiosis and possible implications in other developmental processes.

Keywords: CDC14; PP2A; cell cycle; gene expression; protein phosphorylation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Dual-Specificity Phosphatases / genetics
  • Dual-Specificity Phosphatases / metabolism
  • Humans
  • Mice
  • Mitosis
  • Phosphorylation
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Protein Tyrosine Phosphatases
  • Dual-Specificity Phosphatases
  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • CDC14B protein, human
  • CDC14A protein, mouse
  • CDC14 protein, S cerevisiae