RRC ID 76092
Author Wu C, Karakuzu O, Garsin DA.
Title Tribbles pseudokinase NIPI-3 regulates intestinal immunity in Caenorhabditis elegans by controlling SKN-1/Nrf activity.
Journal Cell Rep
Abstract In Caenorhabditis elegans, ROS generated in response to intestinal infection induces SKN-1, a protective transcription factor homologous to nuclear factor erythroid 2-related factor 1 or 2 (NRF1/2) in mammals. Many factors regulate SKN-1, including the p38 mitogen-activated protein kinase (MAPK) cascade that activates SKN-1 by phosphorylation. In this work, another positive regulator of SKN-1 is identified: NIPI-3, a Tribbles pseudokinase. NIPI-3 has been reported to protect against intestinal infection by negatively regulating the CCAT enhancer binding protein (C/EBP) bZIP transcription factor CEBP-1. Here we demonstrate that CEBP-1 positively regulates the vhp-1 transcript, which encodes a phosphatase that dephosphorylates the p38 MAPK called PMK-1. The increased levels of VHP-1 caused by CEBP-1 transcriptional enhancement result in less PMK-1 phosphorylation, affecting SKN-1 activity and intestinal resistance to the pathogen. The data support a model in which NIPI-3's negative regulation of CEBP-1 decreases VHP-1 phosphatase activity, allowing increased stimulation of SKN-1 activity by the p38 MAPK phosphorylation cascade in the intestine.
Volume 36(7)
Pages 109529
Published 2021-8-17
DOI 10.1016/j.celrep.2021.109529
PII S2211-1247(21)00960-8
PMID 34407394
PMC PMC8393239
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / metabolism* Feedback, Physiological Gene Expression Regulation Immunity, Innate* Intestines / immunology* Protein Kinases / genetics Protein Kinases / metabolism* Transcription Factors / metabolism*
Resource
C.elegans tm2807