Alicja Sznarkowska, Anna Kostecka, Anna Kawiak, Pilar Acedo, Mattia Lion, Alberto Inga, Joanna Zawacka-Pankau
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引用次数: 12
Abstract
Background: The p73 protein is a tumor suppressor that shares structural and functional similarity with p53. p73 is expressed in two major isoforms; the TA isoform that interacts with p53 pathway, thus acting as tumor suppressor and the N-terminal truncated ΔN isoform that inhibits TAp73 and p53 and thus, acts as an oncogene.
Results: By employing a drug repurposing approach, we found that protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid applied in photodynamic therapy of cancer, stabilizes TAp73 and activates TAp73-dependent apoptosis in cancer cells lacking p53. The mechanism of TAp73 activation is via disruption of TAp73/MDM2 and TAp73/MDMX interactions and inhibition of TAp73 degradation by ubiquitin ligase Itch. Finally, PpIX showed potent antitumor effect and inhibited the growth of xenograft human tumors in mice.
Conclusion: Our findings may in future contribute to the successful repurposing of PpIX into clinical practice.
期刊介绍：
Cell Division is an open access, peer-reviewed journal that encompasses all the molecular aspects of cell cycle control and cancer, cell growth, proliferation, survival, differentiation, signalling, gene transcription, protein synthesis, genome integrity, chromosome stability, centrosome duplication, DNA damage and DNA repair.
Cell Division provides an online forum for the cell-cycle community that aims to publish articles on all exciting aspects of cell-cycle research and to bridge the gap between models of cell cycle regulation, development, and cancer biology. This forum is driven by specialized and timely research articles, reviews and commentaries focused on this fast moving field, providing an invaluable tool for cell-cycle biologists.
Cell Division publishes articles in areas which includes, but not limited to:
DNA replication, cell fate decisions, cell cycle & development
Cell proliferation, mitosis, spindle assembly checkpoint, ubiquitin mediated degradation
DNA damage & repair
Apoptosis & cell death
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