title: Retrograde signaling from autophagy modulates stress responses.
abstract: Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFκB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and "signalphagy," which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses.
authors.affiliation: Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland. hus@pki.unibe.ch.
authors.forename: Hans-Uwe
authors.identifier: 0000-0002-9404-7736
authors.initials: HU
authors.lastname: Simon
authors.affiliation: Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
authors.forename: Robert
authors.identifier: 0000-0002-5461-4855
authors.initials: R
authors.lastname: Friis
authors.affiliation: Cancer Research U.K. Beatson Institute, Glasgow G61 1BD, U.K.
authors.forename: Stephen W G
authors.identifier: 0000-0001-7697-132X
authors.initials: SW
authors.lastname: Tait
authors.affiliation: Cancer Research U.K. Beatson Institute, Glasgow G61 1BD, U.K.
authors.forename: Kevin M
authors.identifier: 0000-0002-1059-9681
authors.initials: KM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008954:Models, Biological; D060066:Protein Interaction Maps; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors