Abstract
The p53 tumor suppressor is recognized as a promising target for anti-cancer therapies. We previously reported that protoporphyrin IX (PpIX) disrupts the p53/murine double minute 2 (MDM2) complex and leads to p53 accumulation and activation of apoptosis in HCT 116 cells. Here we show the direct binding of PpIX to the N-terminal domain of p53. Furthermore, we addressed the induction of apoptosis in HCT 116 p53-null cells by PpIX and revealed interactions between PpIX and p73. We propose that PpIX disrupts the p53/MDM2 or MDMX and p73/MDM2 complexes and thereby activates the p53- or p73-dependent cancer cell death.
Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis / drug effects
-
Binding Sites / genetics
-
Cell Cycle Proteins
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Electrophoresis, Polyacrylamide Gel
-
Fluorescence Polarization / methods
-
Glutathione Transferase / genetics
-
Glutathione Transferase / metabolism
-
HCT116 Cells
-
Humans
-
Mutation
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism*
-
Protein Binding / drug effects
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism
-
Proto-Oncogene Proteins c-mdm2 / genetics
-
Proto-Oncogene Proteins c-mdm2 / metabolism
-
Protoporphyrins / metabolism*
-
Protoporphyrins / pharmacology
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Tumor Protein p73
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / metabolism*
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism*
Substances
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
MDM4 protein, human
-
Nuclear Proteins
-
Proto-Oncogene Proteins
-
Protoporphyrins
-
Recombinant Fusion Proteins
-
TP73 protein, human
-
Tumor Protein p73
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
protoporphyrin IX
-
MDM2 protein, human
-
Proto-Oncogene Proteins c-mdm2
-
Glutathione Transferase