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Regulation of autophagy by cytoplasmic p53.

Tasdemir, Ezgi (author)
Maiuri, M Chiara (author)
Galluzzi, Lorenzo (author)
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Vitale, Ilio (author)
Djavaheri-Mergny, Mojgan (author)
D'Amelio, Marcello (author)
Criollo, Alfredo (author)
Morselli, Eugenia (author)
Zhu, Changlian, 1964 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Harper, Francis (author)
Nannmark, Ulf, 1958 (author)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Samara, Chrysanthi (author)
Pinton, Paolo (author)
Vicencio, José Miguel (author)
Carnuccio, Rosa (author)
Moll, Ute M (author)
Madeo, Frank (author)
Paterlini-Brechot, Patrizia (author)
Rizzuto, Rosario (author)
Szabadkai, Gyorgy (author)
Pierron, Gérard (author)
Blomgren, Klas, 1963 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institutionen för kliniska vetenskaper,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Institute of Clinical Sciences
Tavernarakis, Nektarios (author)
Codogno, Patrice (author)
Cecconi, Francesco (author)
Kroemer, Guido (author)
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 (creator_code:org_t)
2008-05-04
2008
English.
In: Nature cell biology. - : Springer Science and Business Media LLC. - 1476-4679 .- 1465-7392. ; 10:6, s. 676-87
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Animals
Anoxia
Autophagy
Cell Line
Tumor
Cytoplasm
metabolism
Endoplasmic Reticulum
metabolism
Gene Expression Regulation
Genes
p53
Humans
Lysosomes
metabolism
Mice
Mice
Transgenic
Models
Biological
Proteasome Endopeptidase Complex
metabolism
Tumor Suppressor Protein p53
metabolism
physiology

Publication and Content Type

ref (subject category)
art (subject category)

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