title: Regulation of autophagy by cytoplasmic p53.
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.
authors.affiliation: INSERM, U848, France.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Tasdemir
authors.forename: M Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Mojgan
authors.initials: M
authors.lastname: Djavaheri-Mergny
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Eugenia
authors.initials: E
authors.lastname: Morselli
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.forename: Francis
authors.initials: F
authors.lastname: Harper
authors.forename: Ulf
authors.initials: U
authors.lastname: Nannmark
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Samara
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Vicencio
authors.forename: Rosa
authors.initials: R
authors.lastname: Carnuccio
authors.forename: Ute M
authors.initials: UM
authors.lastname: Moll
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Paterlini-Brechot
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Szabadkai
authors.forename: Gérard
authors.initials: G
authors.lastname: Pierron
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.forename: Nektarios
authors.initials: N
authors.lastname: Tavernarakis
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D000860:Hypoxia; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D046988:Proteasome Endopeptidase Complex