RIP1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis

EMBO Rep. 2015 Jun;16(6):700-8. doi: 10.15252/embr.201439496. Epub 2015 Apr 23.


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.

Keywords: RIP1 (RIPK1); ERK; TFEB; autophagy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Autophagy*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cells, Cultured
  • Fibroblasts
  • Gene Expression Regulation*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Lysosomes / genetics
  • Mice
  • Phosphorylation / physiology
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Transcription Factors / metabolism


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFEB protein, human
  • Transcription Factors
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse