Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

DOI

10.1016/j.molcel.2008.11.019

Type

Journal article

Journal

Mol Cell

Publication Date

26/12/2008

Volume

32

Pages

803 - 814

Keywords

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