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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)803-814
Number of pages12
JournalMolecular Cell
Volume32
Issue number6
DOIs
Publication statusPublished - Dec 26 2008

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Leukemia
DNA Damage
Proteins
Sumoylation
Tumor Suppressor Genes
Transcriptional Activation
Neoplasms
Phosphotransferases
Apoptosis
Tumor Protein p73
Promyelocytic Leukemia Protein

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop. / Lapi, Eleonora; Di Agostino, Silvia; Donzelli, Sara; Gal, Hilah; Domany, Eytan; Rechavi, Gideon; Pandolfi, Pier Paolo; Givol, David; Strano, Sabrina; Lu, Xin; Blandino, Giovanni.

In: Molecular Cell, Vol. 32, No. 6, 26.12.2008, p. 803-814.

Research output: Contribution to journalArticle

Lapi, E, Di Agostino, S, Donzelli, S, Gal, H, Domany, E, Rechavi, G, Pandolfi, PP, Givol, D, Strano, S, Lu, X & Blandino, G 2008, 'PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop', Molecular Cell, vol. 32, no. 6, pp. 803-814. https://doi.org/10.1016/j.molcel.2008.11.019
Lapi E, Di Agostino S, Donzelli S, Gal H, Domany E, Rechavi G et al. PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop. Molecular Cell. 2008 Dec 26;32(6):803-814. https://doi.org/10.1016/j.molcel.2008.11.019
Lapi, Eleonora ; Di Agostino, Silvia ; Donzelli, Sara ; Gal, Hilah ; Domany, Eytan ; Rechavi, Gideon ; Pandolfi, Pier Paolo ; Givol, David ; Strano, Sabrina ; Lu, Xin ; Blandino, Giovanni. / PML, YAP, and p73 Are Components of a Proapoptotic Autoregulatory Feedback Loop. In: Molecular Cell. 2008 ; Vol. 32, No. 6. pp. 803-814.
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AU - Domany, Eytan

AU - Rechavi, Gideon

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