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

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

Author information

1
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
2
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
3
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA University of Colorado Comprehensive Cancer Center, Aurora, CO, USA.
4
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.

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.

KEYWORDS:

RIP1 (RIPK1); ERK; TFEB; autophagy

Comment in

PMID:
25908842
PMCID:
PMC4467854
DOI:
10.15252/embr.201439496
[Indexed for MEDLINE]
Free PMC Article

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