PRIMA-1(MET) induces nucleolar accumulation of mutant p53 and PML nuclear body-associated proteins

Oncogene. 2007 Feb 15;26(7):982-92. doi: 10.1038/sj.onc.1209858. Epub 2006 Aug 14.


We have previously identified PRIMA-1, a low molecular weight compound that restores the transcriptional transactivation function to mutant p53 and induction of apoptosis. To explore the molecular mechanism for PRIMA-1-induced mutant p53-dependent apoptosis, we examined the intracellular distribution of mutant p53 upon treatment with PRIMA-1(MET) by immunofluorescence staining. We found that PRIMA-1(MET) induced nucleolar translocation of mutant p53 and the promyelocytic leukemia (PML) nuclear body-associated proteins PML, CBP and Hsp70. Levels of Hsp70 were significantly enhanced by PRIMA-1(MET) treatment. PRIMA-Dead, a compound structurally related to PRIMA-1 but unable to induce mutant p53-dependent apoptosis, failed to induce nucleolar translocation of mutant p53. Our results suggest that redistribution of mutant p53 to nucleoli plays a role in PRIMA-1-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Apoptosis / genetics
  • Aza Compounds / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Line, Tumor
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • DNA Methylation
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • PML protein, human
  • 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one