Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

FEBS Lett. 2019 Oct;593(20):2908-2924. doi: 10.1002/1873-3468.13595. Epub 2019 Sep 18.

Abstract

Here, we will review the evidence showing that mitotic exit is initiated by regulated proteolysis and then driven by the PPP family of phosphoserine/threonine phosphatases. Rapid APC/CCDC20 and ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid separation, the first step of mitotic exit. Because proteolysis of Aurora and Polo family kinases dependent on APC/CCDH1 is relatively slow, this creates a new regulatory state, anaphase, different to G2 and M-phase. We will discuss how the CDK1-counteracting phosphatases PP1 and PP2A-B55, together with Aurora and Polo kinases, contribute to the temporal regulation and order of events in the different stages of mitotic exit from anaphase to cytokinesis. For PP2A-B55, these timing properties are created by the ENSA-dependent inhibitory pathway and differential recognition of phosphoserine and phosphothreonine. Finally, we will discuss how Aurora B and PP2A-B56 are needed for the spatial regulation of anaphase spindle formation and how APC/C-dependent destruction of PLK1 acts as a timer for abscission, the final event of cytokinesis.

Keywords: cell cycle; kinase; mitosis; mitotic exit; phosphatase; proteolysis.

Publication types

  • Review

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / genetics*
  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cdc20 Proteins / genetics*
  • Cdc20 Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cytokinesis / genetics
  • Gene Expression Regulation
  • Humans
  • M Phase Cell Cycle Checkpoints*
  • Polo-Like Kinase 1
  • Protein Phosphatase 1 / genetics*
  • Protein Phosphatase 1 / metabolism
  • Protein Phosphatase 2 / genetics*
  • Protein Phosphatase 2 / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Securin / genetics
  • Securin / metabolism
  • Signal Transduction
  • Spatio-Temporal Analysis

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • Proto-Oncogene Proteins
  • Securin
  • pituitary tumor-transforming protein 1, human
  • CDC20 protein, human
  • Anaphase-Promoting Complex-Cyclosome
  • AURKA protein, human
  • Aurora Kinase A
  • Protein Serine-Threonine Kinases
  • PP2A-B56alpha protein, human
  • Protein Phosphatase 1
  • Protein Phosphatase 2