Abstract
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*
Substances
-
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