Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop.

Molecular cell | Dec 26, 2008

http://www.ncbi.nlm.nih.gov/pubmed/19111660

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.

Pubmed ID: 19111660 RIS Download

Mesh terms: 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 | 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

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.