RIP1 negatively regulates basal autophagic flux through TFEB to control sensitivity to apoptosis. (23rd April 2015)

• Record Type: Journal Article
• Authors: Yonekawa, Tohru; Gamez, Graciela; Kim, Jihye; Tan, Aik Choon; Thorburn, Jackie; Gump, Jacob; Thorburn, Andrew; Morgan, Michael J
• Is Part Of: EMBO reports. Volume 16:Number 6(2015:Jun.)
• Page Start: 700
• Page End: 708
• Publication Date: 2015-04-23
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201439496
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201439496-abs-0001"> <title>Abstract</title> <p>In a synthetic lethality/viability screen, we identified the serine–threonine kinase RIP1 (RIPK1) as a gene whose knockdown is highly selected <italic>against</italic> during growth in normal media, in which autophagy is not critical, but selected <italic>for</italic> 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.</p> </abstract>