PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop
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 proapopto...
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Published in: | Molecular cell Vol. 32; no. 6; pp. 803 - 814 |
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Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Elsevier Inc
26-12-2008
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Subjects: | |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1097-2765 1097-4164 |
DOI: | 10.1016/j.molcel.2008.11.019 |