title: RIP1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis.
abstract: In a synthetic lethality/viability screen, we identified the serine-threonine kinase RIP1 (RIPK1) as a gene whose knockdown is highly selected against during growth in normal media, in which autophagy is not critical, but selected for in conditions that increase reliance on basal autophagy. RIP1 represses basal autophagy in part due to its ability to regulate the TFEB transcription factor, which controls the expression of autophagy-related and lysosomal genes. RIP1 activates ERK, which negatively regulates TFEB though phosphorylation of serine 142. Thus, in addition to other pro-death functions, RIP1 regulates cellular sensitivity to pro-death stimuli by modulating basal autophagy.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yonekawa
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Graciela
authors.initials: G
authors.lastname: Gamez
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Aik Choon
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Thorburn
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Gump
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA University of Colorado Comprehensive Cancer Center, Aurora, CO, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thorburn
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA University of Colorado Comprehensive Cancer Center, Aurora, CO, USA michael.morgan@ucdenver.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morgan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000235:genetics; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064972:TFEB protein, human; D014157:Transcription Factors; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse
keywords:   RIP1 (RIPK1); ERK; TFEB; autophagy