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PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop

Molecular Cell, ISSN: 1097-2765, Vol: 32, Issue: 6, Page: 803-814
2008
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Article Description

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.

Bibliographic Details

Lapi, Eleonora; Di Agostino, Silvia; Donzelli, Sara; Gal, Hilah; Domany, Eytan; Rechavi, Gideon; Pandolfi, Pier Paolo; Givol, David; Strano, Sabrina; Lu, Xin; Blandino, Giovanni

Elsevier BV

Biochemistry, Genetics and Molecular Biology

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