Abstract：
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Lapi E,Di Agostino S,Donzelli S,Gal H,Domany E,Rechavi G,Pandolfi PP,Givol D,Strano S,Lu X,Blandino Gdoi
10.1016/j.molcel.2008.11.019subject
Has Abstractpub_date
2008-12-26 00:00:00pages
803-14issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(08)00841-1journal_volume
32pub_type
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