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p73 has been identified as a structural and functional homolog of the tumor suppressor p53. The transcriptional coactivator Yes-associated protein (YAP) has been demonstrated to interact with and to enhance p73-dependent apoptosis in response to DNA damage. Here, we show the existence of a proapoptotic autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia (PML) tumor suppressor gene. We demonstrate that PML is a direct transcriptional target of p73/YAP, and we show that PML transcriptional activation by p73/YAP is under the negative control of the proto-oncogenic Akt/PKB kinase. Importantly, we find that PML and YAP physically interact through their PVPVY and WW domains, respectively, causing PML-mediated sumoylation and stabilization of YAP. Hence, we determine a mechanistic pathway in response to DNA damage that could have relevant implications for the treatment of human cancer.

Original publication




Journal article


Mol Cell

Publication Date





803 - 814


Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Cell Line, Cisplatin, DNA-Binding Proteins, Feedback, Physiological, Gene Expression Regulation, Neoplastic, Humans, Mice, Models, Biological, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Phosphoproteins, Promyelocytic Leukemia Protein, Proteasome Endopeptidase Complex, Protein Binding, Protein Processing, Post-Translational, Protein Stability, Regulatory Sequences, Nucleic Acid, Small Ubiquitin-Related Modifier Proteins, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Proteins, Ubiquitin