Open AccessCell competition is driven by Xrp1-mediated phosphorylation of eukaryotic initiation factor 2α
Author(s) -
Naotaka Ochi,
Mitsuki Nakamura,
Rigata,
Naoki Wakasa,
Ryuichi Nakano,
Tatsushi Igaki
Publication year - 2021
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009958
Subject(s) - biology , microbiology and biotechnology , cell , phosphorylation , unfolded protein response , initiation factor , eukaryotic initiation factor , endoplasmic reticulum , transcription factor , protein kinase a , genetics , rna , ribosome , gene
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.