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Functional role of autophagy-mediated proteome remodeling in cell survival signaling and innate immunity.

Abstract
Ras-driven cancer cells upregulate basal autophagy that degrades and recycles intracellular proteins and organelles. Autophagy-mediated proteome degradation provides free amino acids to support metabolism and macromolecular synthesis, which confers a survival advantage in starvation and promotes tumorigenesis. While the degradation of isolated protein substrates by autophagy has been implicated in controlling cellular function, the extent and specificity by which autophagy remodels the cellular proteome and the underlying functional consequences were unknown. Here we compared the global proteome of autophagy-functional and -deficient Ras-driven cancer cells, finding that autophagy affects the majority of the proteome yet is highly selective. While levels of vesicle trafficking proteins important for autophagy are preserved during starvation-induced autophagy, deleterious inflammatory response pathway components are eliminated even under basal conditions, preventing cytokine-induced paracrine cell death. This reveals the global, functional impact of autophagy-mediated proteome remodeling on cell survival and identifies critical autophagy substrates that mediate this process.
AuthorsRobin Mathew, Sinan Khor, Sean R Hackett, Joshua D Rabinowitz, David H Perlman, Eileen White
JournalMolecular cell (Mol Cell) Vol. 55 Issue 6 Pg. 916-930 (Sep 18 2014) ISSN: 1097-4164 [Electronic] United States
PMID25175026 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Proteome
  • ras Proteins
Topics
  • Animals
  • Autophagy
  • Cell Line, Tumor
  • Cell Survival
  • Humans
  • Immunity, Innate
  • Mice
  • Protein Transport
  • Proteome (physiology)
  • Transport Vesicles
  • ras Proteins (genetics)

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