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p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200.

Authors
  • Morselli, Eugenia
  • Shen, Shensi
  • Ruckenstuhl, Christoph
  • Bauer, Maria Anna
  • Mariño, Guillermo
  • Galluzzi, Lorenzo
  • Criollo, Alfredo
  • Michaud, Mickael
  • Maiuri, Maria Chiara
  • Chano, Tokuhiro
  • Madeo, Frank
  • Kroemer, Guido
Type
Published Article
Journal
Cell Cycle
Publisher
Landes Bioscience
Publication Date
Aug 15, 2011
Volume
10
Issue
16
Pages
2763–2769
Identifiers
PMID: 21775823
Source
Medline
License
Unknown

Abstract

The tumor suppressor protein p53 tonically suppresses autophagy when it is present in the cytoplasm. This effect is phylogenetically conserved from mammals to nematodes, and human p53 can inhibit autophagy in yeast, as we show here. Bioinformatic investigations of the p53 interactome in relationship to the autophagy-relevant protein network underscored the possible relevance of a direct molecular interaction between p53 and the mammalian ortholog of the essential yeast autophagy protein Atg17, namely RB1-inducible coiled-coil protein 1 (RB1CC1), also called FAK family kinase-interacting protein of 200 KDa (FIP200). Mutational analyses revealed that a single point mutation in p53 (K382R) abolished its capacity to inhibit autophagy upon transfection into p53-deficient human colon cancer or yeast cells. In conditions in which wild-type p53 co-immunoprecipitated with RB1CC1/FIP200, p53 (K382R) failed to do so, underscoring the importance of the physical interaction between these proteins for the control of autophagy. In conclusion, p53 regulates autophagy through a direct molecular interaction with RB1CC1/FIP200, a protein that is essential for the very apical step of autophagy initiation.

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