Targeting of p53 and its homolog p73 by protoporphyrin IX |
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| Authors: | Sznarkowska Alicja Maleńczyk Katarzyna Kadziński Leszek Bielawski Krzysztof P Banecki Bogdan Zawacka-Pankau Joanna |
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| Affiliation: | aDepartment of Biotechnology, Laboratory of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk & Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland;bDepartment of Molecular and Cellular Biology, Laboratory of Physical Biochemistry, Intercollegiate Faculty of Biotechnology, University of Gdansk & Medical University of Gdansk, Kladki 24, 80-822 Gdansk, Poland |
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| 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. |
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| Keywords: | Abbreviations: aa, amino acid 5-ALA, 5-aminolevulinic acid FP, fluorescence polarisation HSA, human serum albumin MDM2, murine double minute 2 N, NH2-terminal dN, delta N-terminal PAGE, polyacrylamide gel electrophoresis PDT, photodynamic therapy RITA, reactivation of p53 and induction of tumor cells apoptosis wt-p53, wild-type p53 |
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