SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response.
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.
An
Jae Hyung
JH
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Blackwell
T Keith
TK
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004707:Endoderm / Q000378:metabolism*; D007422:Intestines / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C073702:skn-1 protein, C elegans; D004247:DNA; D010269:Paraquat