Critical role of the nucleolus in activation of the p53-dependent postmitotic checkpoint

Biochem Biophys Res Commun. 2011 Apr 8;407(2):378-82. doi: 10.1016/j.bbrc.2011.03.029. Epub 2011 Mar 21.


Cells eventually exit from mitosis during sustained arrest at the spindle checkpoint, without sister chromatid separation and cytokinesis. The resulting tetraploid cells are arrested in the subsequent G1 phase in a p53-dependent manner by the regulatory function of the postmitotic G1 checkpoint. Here we report how the nucleolus plays a critical role in activation of the postmitotic G1 checkpoint. During mitosis, the nucleolus is disrupted and many nucleolar proteins are translocated from the nucleolus into the cytoplasm. Among the nucleolar factors, Myb-binding protein 1a (MYBBP1A) induces the acetylation and accumulation of p53 by enhancing the interaction between p300 and p53 during prolonged mitosis. MYBBP1A-dependent p53 activation is essential for the postmitotic G1 checkpoint. Thus, our results demonstrate a novel nucleolar function that monitors the prolongation of mitosis and converts its signal into activation of the checkpoint machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Active Transport, Cell Nucleus / drug effects
  • Cell Line, Tumor
  • Cell Nucleolus / metabolism*
  • DNA-Binding Proteins
  • G1 Phase*
  • Gene Knockdown Techniques
  • Humans
  • Mitosis
  • Nocodazole / pharmacology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Polyploidy
  • RNA-Binding Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • p300-CBP Transcription Factors / metabolism


  • DNA-Binding Proteins
  • MYBBP1A protein, human
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • RNA-Binding Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • p300-CBP Transcription Factors
  • Nocodazole