title: Signaling networks converge on TORC1-SREBP activity to promote endoplasmic reticulum homeostasis.
abstract: The function and capacity of the endoplasmic reticulum (ER) is determined by multiple processes ranging from the local regulation of peptide translation, translocation, and folding, to global changes in lipid composition. ER homeostasis thus requires complex interactions amongst numerous cellular components. However, describing the networks that maintain ER function during changes in cell behavior and environmental fluctuations has, to date, proven difficult. Here we perform a systems-level analysis of ER homeostasis, and find that although signaling networks that regulate ER function have a largely modular architecture, the TORC1-SREBP signaling axis is a central node that integrates signals emanating from different sub-networks. TORC1-SREBP promotes ER homeostasis by regulating phospholipid biosynthesis and driving changes in ER morphology. In particular, our network model shows TORC1-SREBP serves to integrate signals promoting growth and G1-S progression in order to maintain ER function during cell proliferation.
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sanchez-Alvarez
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Fabian
authors.initials: F
authors.lastname: Finger
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Maria del Mar
authors.initials: Mdel M
authors.lastname: Arias-Garcia
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Vicky
authors.initials: V
authors.lastname: Bousgouni
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pascual-Vargas
authors.affiliation: Division of Cancer Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Bakal
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress; D004722:Endoribonucleases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000502:physiology; D059585:G1 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D050356:Lipid Metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: D029721:Drosophila Proteins; D005231:Fatty Acids, Unsaturated; D051779:Sterol Regulatory Element Binding Proteins; C570998:TORC1 protein complex, Drosophila; D014157:Transcription Factors; D004722:Endoribonucleases; C511918:inositol requiring enzyme-1, Drosophila