title: Targeting of p53 and its homolog p73 by protoporphyrin IX.
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.
authors.affiliation: Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk & Medical University of Gdansk, Gdansk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Sznarkowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maleńczyk
authors.forename: Leszek
authors.initials: L
authors.lastname: Kadziński
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Bielawski
authors.forename: Bogdan
authors.initials: B
authors.lastname: Banecki
authors.forename: Joanna
authors.initials: J
authors.lastname: Zawacka-Pankau
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005454:Fluorescence Polarization / Q000379:methods; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011524:Protoporphyrins; D011993:Recombinant Fusion Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C028025:protoporphyrin IX; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D005982:Glutathione Transferase