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Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status
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Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status
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Journal Article
Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status
2021
Overview
Cell competition induces the elimination of less-fit “loser” cells by fitter “winner” cells. In Drosophila , cells heterozygous mutant in ribosome genes, Rp/+ , known as Minutes , are outcompeted by wild-type cells. Rp/+ cells display proteotoxic stress and the oxidative stress response, which drive the loser status. Minute cell competition also requires the transcription factors Irbp18 and Xrp1, but how these contribute to the loser status is partially understood. Here we provide evidence that initial proteotoxic stress in RpS3/+ cells is Xrp1-independent. However, Xrp1 is sufficient to induce proteotoxic stress in otherwise wild-type cells and is necessary for the high levels of proteotoxic stress found in RpS3/+ cells. Surprisingly, Xrp1 is also induced downstream of proteotoxic stress, and is required for the competitive elimination of cells suffering from proteotoxic stress or overexpressing Nrf2. Our data suggests that a feed-forward loop between Xrp1, proteotoxic stress, and Nrf2 drives Minute cells to become losers.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ DNA-Binding Proteins - genetics
/ Drosophila melanogaster - genetics
/ Drosophila Proteins - genetics
/ Gene Expression Regulation, Developmental - genetics
/ Genes
/ Identification and classification
/ Imaginal Discs - growth & development
/ Leucine
/ Research and Analysis Methods
/ Ribosomal Proteins - genetics
