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PMID: 12869585 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.

Genes & development ·Vol. 17 ·No. 15 ·2003-08-01 ·Pages 1882-93

An JH, Blackwell TK

Abstract

During the earliest stages of Caenorhabditis elegans embryogenesis, the transcription factor SKN-1 initiates development of the digestive system and other mesendodermal tissues. Postembryonic SKN-1 functions have not been elucidated. SKN-1 binds to DNA through a unique mechanism, but is distantly related to basic leucine-zipper proteins that orchestrate the major oxidative stress response in vertebrates and yeast. Here we show that despite its distinct mode of target gene recognition, SKN-1 functions similarly to resist oxidative stress in C. elegans. During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively. SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress. skn-1 mutants are sensitive to oxidative stress and have shortened lifespans. SKN-1 represents a connection between developmental specification of the digestive system and one of its most basic functions, resistance to oxidative and xenobiotic stress. This oxidative stress response thus appears to be both widely conserved and ancient, suggesting that the mesendodermal specification role of SKN-1 was predated by its function in these detoxification mechanisms.

MeSH Terms
Amino Acid Motifs Animals Base Sequence Binding Sites Caenorhabditis elegans/metabolism Caenorhabditis elegans Proteins/genetics,physiology Cell Nucleus/metabolism DNA/metabolism DNA-Binding Proteins/genetics,physiology Endoderm/metabolism Intestines/embryology Mesoderm/metabolism Microscopy, Fluorescence Models, Biological Models, Genetic Molecular Sequence Data Mutation Oxidative Stress Paraquat/pharmacology Plasmids/metabolism Protein Binding Time Factors Transcription Factors/genetics,physiology Transgenes
Chemicals
Caenorhabditis elegans Proteins DNA-Binding Proteins Transcription Factors skn-1 protein, C elegans DNA Paraquat
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
An Jae Hyung
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Blackwell T Keith
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1107803
Published
2003-08-01
Epub
2003-00-17
Pages
1882-93
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196237
Subset
IM
Grants
NIGMS NIH HHS · R01 GM062891 · United States
NIGMS NIH HHS · GM62891 · United States
External Links
PubMed source DOI: 10.1101/gad.1107803 PMC Full Text View journal details
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