LIN-3/EGF Promotes the Programmed Cell Death of Specific Cells in Caenorhabditis elegans by Transcriptional Activation of the Pro-apoptotic Gene egl-1
Journal
Plos Genetics
Journal Volume
10
Journal Issue
10
Date Issued
2014
Author(s)
Jiang, Hang-Shiang
Abstract
Programmed cell death (PCD) is the physiological death of a cell mediated by an intracellular suicide program. Although key components of the PCD execution pathway have been identified, how PCD is regulated during development is poorly understood. Here, we report that the epidermal growth factor (EGF)-like ligand LIN-3 acts as an extrinsic signal to promote the death of specific cells in Caenorhabditis elegans. The loss of LIN-3 or its receptor, LET-23, reduced the death of these cells, while excess LIN-3 or LET-23 signaling resulted in an increase in cell deaths. Our molecular and genetic data support the model that the LIN-3 signal is transduced through LET-23 to activate the LET-60/RAS-MPK-1/ERK MAPK pathway and the downstream ETS domain-containing transcription factor LIN-1. LIN-1 binds to, and activates transcription of, the key pro-apoptotic gene egl-1, which leads to the death of specific cells. Our results provide the first evidence that EGF induces PCD at the whole organism level and reveal the molecular basis for the death-promoting function of LIN-3/EGF. In addition, the level of LIN-3/EGF signaling is important for the precise fine-tuning of the life-versus-death fate. Our data and the previous cell culture studies that say EGF triggers apoptosis in some cell lines suggest that the EGF-mediated modulation of PCD is likely conserved in C. elegans and humans. ? 2014 Jiang, Wu.
SDGs
Other Subjects
epidermal growth factor receptor; let 23 protein; let 60 protein; lin 1 protein; lin 3 protein; lin 31 protein; mitogen activated protein kinase; mpk 1 protein; Ras protein; RNA; unclassified drug; Caenorhabditis elegans protein; EGL-1 protein, C elegans; epidermal growth factor; epidermal growth factor receptor; let-23 protein, C elegans; Lin-1 protein, C elegans; Lin-3 protein, C elegans; repressor protein; transcription factor; animal cell; animal experiment; apoptosis; Article; Caenorhabditis elegans; controlled study; egl 1 gene; embryo; genetic transcription; genotype; microbial gene; nonhuman; protein binding; protein expression; protein function; protein protein interaction; RNA interference; signal transduction; transcription initiation; upregulation; wild type; animal; biosynthesis; Caenorhabditis elegans; cell death; cell lineage; gene expression regulation; genetics; human; metabolism; transcription initiation; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Death; Cell Lineage; Epidermal Growth Factor; Gene Expression Regulation, Developmental; Humans; MAP Kinase Signaling System; Receptor, Epidermal Growth Factor; Repressor Proteins; Transcription Factors; Transcriptional Activation
Type
journal article