RRC ID 76234
Author Malinow RA, Zhu M, Jin Y, Kim KW.
Title Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development.
Journal Sci Rep
Abstract Coordinating the balance between development and stress responses is critical for organismal survival. However, the cellular signaling controlling this mechanism is not well understood. In Caenorhabditis elegans, it has been hypothesized that a genetic network regulated by NIPI-3/Tibbles may control the balance between animal development and immune response. Using a nipi-3(0) lethality suppressor screen in C. elegans, we reveal a novel role for N-terminal acetyltransferase C complex natc-1/2/3 and histone deacetylase hda-4, in the control of animal development. These signaling proteins act, at least in part, through a PMK-1 p38 MAP kinase pathway (TIR-1-NSY-1-SEK-1-PMK-1), which plays a critical role in the innate immunity against infection. Additionally, using a transcriptional reporter of SEK-1, a signaling molecule within this p38 MAP kinase system that acts directly downstream of C/EBP bZip transcription factor CEBP-1, we find unexpected positive control of sek-1 transcription by SEK-1 along with several other p38 MAP kinase pathway components. Together, these data demonstrate a role for NIPI-3 regulators in animal development, operating, at least in part through a PMK-1 p38 MAPK pathway. Because the C. elegans p38 MAP kinase pathway is well known for its role in cellular stress responses, the novel biological components and mechanisms pertaining to development identified here may also contribute to the balance between stress response and development.
Volume 12(1)
Pages 16438
Published 2022-9-30
DOI 10.1038/s41598-022-20361-x
PII 10.1038/s41598-022-20361-x
PMID 36180459
PMC PMC9525577
MeSH Animals Basic-Leucine Zipper Transcription Factors / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Gene Regulatory Networks Genetic Testing Histone Deacetylases / genetics Histone Deacetylases / metabolism Imidazoles Immunity, Innate MAP Kinase Signaling System N-Terminal Acetyltransferase C / genetics N-Terminal Acetyltransferase C / metabolism Nitriles Protein Kinases / metabolism p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism
C.elegans tm2807 tm2927