biostudies-literatureGabaldon CNational Institute of Allergy and Infectious DiseasesNIAID NIH HHSNational Institutes of HealthNIH HHSiyae131https://www.ebi.ac.uk/biostudies/studies/S-EPMC11538416biostudies-literatureUnknown228(3)During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 activation on pathogen and we sought to understand the mechGeneticsSKN-1 activation during infection of Caenorhabditis elegans requires CDC-48 and endoplasmic reticulum proteostasis.PMC11538416R01AI150045R01 AI150045Garsin DAKarakuzu OGabaldon CfalseSKN-1 activation during infection of Caenorhabditis elegans requires CDC-48 and endoplasmic reticulum proteostasis.During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 activation on pathogen and we sought to understand the mech2024-01-01T00:00:00Z2024 Nov2025-04-04T18:54:46.339Z2025-04-04T18:54:46.339ZS-EPMC115384163916651310.1093/genetics/iyae131