Uncoupling anaphase-promoting complex/cyclosome activity from spindle assembly checkpoint control by deregulating polo-like kinase 1

BCM van de Weerdt, MATM van Vugt, C Lindon, JJW Kauw, MJ Rozendaal, R Klompmaker, RMF Wolthuis, RH Medema*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)

Abstract

Polo-like kinase 1 (Plk1) plays a role in numerous events in mitosis, but how the multiple functions of Plk1 are separated is poorly understood. We studied regulation of Plkl through two putative phosphorylation residues, Ser-137 and Thr-210. Using phospho-specific antibodies, we found that Thr-210 phosphorylation precedes Ser-137 phosphoryllation in vivo, the latter occurring specifically in late mitosis. We show that expression of two activating mutants of these residues, S137D and T210D, results in distinct mitotic phenotypes. Whereas expression of both phospho-mimicking mutants as well as of the double mutant leads to accelerated mitotic entry, further progression through mitosis is dramatically different: the T210D mutant causes a spindle assembly checkpoint-dependent delay, whereas the expression of the S137D mutant or the double mutant results in untimely activation of the anaphase-promoting complex/cyclosome (APC/C) and frequent mitotic catastrophe. Using nonphosphorylatable Plk1-S137A and Plk1-T210A mutants, we show that both sites contribute to proper mitotic progression. Based on these observations, we propose that Plkl function is altered at different stages of mitosis through consecutive posttranslational events, e.g., at Ser-137 and Thr-210. Furthermore, our data show that uncontrolled Plkl activation can uncouple APC/C activity from spindle assembly checkpoint control.

Original languageEnglish
Pages (from-to)2031-2044
Number of pages14
JournalMolecular and Cellular Biology
Volume25
Issue number5
DOIs
Publication statusPublished - Mar-2005
Externally publishedYes

Keywords

  • XENOPUS EGG EXTRACTS
  • CELL-CYCLE
  • MAMMALIAN-CELLS
  • SUBCELLULAR-LOCALIZATION
  • SACCHAROMYCES-CEREVISIAE
  • MITOTIC CATASTROPHE
  • CDC14 LOCALIZATION
  • BIPOLAR SPINDLE
  • PROTEIN-KINASE
  • PLK1

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