Regulation of autophagy by cytoplasmic p53.

@article{citeulike:2776550, abstract = {Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.}, address = {[1] INSERM, U848. [2] Institut Gustave Roussy, Paris 11, 94805 Villejuif, France. [3] Universit\'{e} Paris Sud, Paris 11, 94805 Villejuif, France. [4] These authors contributed equally to this paper.}, author = {Tasdemir, Ezgi and Maiuri, M Chiara C. and Galluzzi, Lorenzo and Vitale, Ilio and Djavaheri-Mergny, Mojgan and D'Amelio, Marcello and Criollo, Alfredo and Morselli, Eugenia and Zhu, Changlian and Harper, Francis and Nannmark, Ulf and Samara, Chrysanthi and Pinton, Paolo and Vicencio, Jos\'{e} Miguel M. and Carnuccio, Rosa and Moll, Ute M M. and Madeo, Frank and Paterlini-Brechot, Patrizia and Rizzuto, Rosario and Szabadkai, Gyorgy and Pierron, G\'{e}rard and Blomgren, Klas and Tavernarakis, Nektarios and Codogno, Patrice and Cecconi, Francesco and Kroemer, Guido }, citeulike-article-id = {2776550}, doi = {10.1038/ncb1730}, issn = {1465-7392}, journal = {Nature cell biology}, keywords = {autophagy}, month = {May}, posted-at = {2008-05-09 21:16:13}, priority = {2}, title = {Regulation of autophagy by cytoplasmic p53.}, url = {http://dx.doi.org/10.1038/ncb1730}, year = {2008} }

TY - JOUR ID - citeulike:2776550 L3 - citeulike-article-id:2776550 TI - Regulation of autophagy by cytoplasmic p53. JF - Nature cell biology AD - [1] INSERM, U848. [2] Institut Gustave Roussy, Paris 11, 94805 Villejuif, France. [3] Université Paris Sud, Paris 11, 94805 Villejuif, France. [4] These authors contributed equally to this paper. SN - 1465-7392 N2 - Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53. KW - autophagy AU - Tasdemir, Ezgi AU - Maiuri, M Chiara AU - Galluzzi, Lorenzo AU - Vitale, Ilio AU - Djavaheri-Mergny, Mojgan AU - D'Amelio, Marcello AU - Criollo, Alfredo AU - Morselli, Eugenia AU - Zhu, Changlian AU - Harper, Francis AU - Nannmark, Ulf AU - Samara, Chrysanthi AU - Pinton, Paolo AU - Vicencio, José Miguel AU - Carnuccio, Rosa AU - Moll, Ute M AU - Madeo, Frank AU - Paterlini-Brechot, Patrizia AU - Rizzuto, Rosario AU - Szabadkai, Gyorgy AU - Pierron, Gérard AU - Blomgren, Klas AU - Tavernarakis, Nektarios AU - Codogno, Patrice AU - Cecconi, Francesco AU - Kroemer, Guido PY - 2008/05/04/ UR - http://dx.doi.org/10.1038/ncb1730 ER -