title: 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.
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, 08854.
authors.forename: Robin
authors.initials: R
authors.lastname: Mathew
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, 08854.
authors.forename: Sinan
authors.initials: S
authors.lastname: Khor
authors.affiliation: Department of Chemistry, and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Hackett
authors.affiliation: Department of Chemistry, and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.affiliation: Department of Molecular Biology, the Lewis-Sigler Institute for Integrative Genomics, and the Princeton Proteomics and Mass Spectrometry Core, Princeton University, Washington Road, Princeton, NJ 08544.
authors.forename: David H
authors.initials: DH
authors.lastname: Perlman
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, 08854. Electronic address: epwhite@cinj.rutgers.edu.
authors.forename: Eileen
authors.initials: E
authors.lastname: White
mesh_terms: D000818:Animals; D001343:Autophagy; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D021381:Protein Transport; D020543:Proteome / Q000502:physiology*; D022161:Transport Vesicles; D018631:ras Proteins / Q000235:genetics*
chemical_list: D020543:Proteome; D018631:ras Proteins