In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2021-12-6), p. e1009958-
Abstract:
Cell competition is a context-dependent cell elimination via cell-cell interaction whereby unfit cells (‘losers’) are eliminated from the tissue when confronted with fitter cells (‘winners’). Despite extensive studies, the mechanism that drives loser’s death and its physiological triggers remained elusive. Here, through a genetic screen in Drosophila , we find that endoplasmic reticulum (ER) stress causes cell competition. Mechanistically, ER stress upregulates the bZIP transcription factor Xrp1, which promotes phosphorylation of the eukaryotic translation initiation factor eIF2α via the kinase PERK, leading to cell elimination. Surprisingly, our genetic data show that different cell competition triggers such as ribosomal protein mutations or RNA helicase Hel25E mutations converge on upregulation of Xrp1, which leads to phosphorylation of eIF2α and thus causes reduction in global protein synthesis and apoptosis when confronted with wild-type cells. These findings not only uncover a core pathway of cell competition but also open the way to understanding the physiological triggers of cell competition.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009958
DOI:
10.1371/journal.pgen.1009958.g001
DOI:
10.1371/journal.pgen.1009958.g002
DOI:
10.1371/journal.pgen.1009958.g003
DOI:
10.1371/journal.pgen.1009958.g004
DOI:
10.1371/journal.pgen.1009958.g005
DOI:
10.1371/journal.pgen.1009958.s001
DOI:
10.1371/journal.pgen.1009958.s002
DOI:
10.1371/journal.pgen.1009958.s003
DOI:
10.1371/journal.pgen.1009958.s004
DOI:
10.1371/journal.pgen.1009958.s005
DOI:
10.1371/journal.pgen.1009958.s006
DOI:
10.1371/journal.pgen.1009958.s007
DOI:
10.1371/journal.pgen.1009958.s008
DOI:
10.1371/journal.pgen.1009958.r001
DOI:
10.1371/journal.pgen.1009958.r002
DOI:
10.1371/journal.pgen.1009958.r003
DOI:
10.1371/journal.pgen.1009958.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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