skn-1-Dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans.
Maintenance of a stable, properly folded, and catalytically active proteome is a major challenge to organisms in the face of multiple internal and external stresses which damage proteins and lead to protein misfolding. Here we show that internal metabolic stress produced by reactive intermediates resulting from tyrosine degradation triggers the expression of the aip-1 gene, which is critical in responses to the environmental toxin arsenic and the clearance of unstable polyglutamine and Abeta proteins. aip-1 acts via binding to the proteosome and enhancing proteosomal function. We find that full induction of aip-1 depends on the oxidative-stress-responsive skn-1 transcription factor but significant induction still occurs without skn-1. Importantly, activation of skn-1 with wdr-23(RNAi), which dramatically induces the expression of other skn-1 target genes, produces a minimal increase in aip-1 expression. This suggests that the previously demonstrated specificity in aip-1/AIRAP induction could reflect the actions of multiple synergistic activators, such as the heat shock factor homolog hsf-1, which we also find is required for full induction. These may be triggered by proteosome dysfunction, as we find that this event links the multiple inducers of aip-1. Together, our results show that cell stress triggers aip-1 expression by both skn-1-dependent and -independent pathways.
Ferguson
Annabel A
AA
University of Pittsburgh, Department of Medicine, Division of Geriatric Medicine, 3471 5th Ave., Suite 500, Pittsburgh, PA 15260, USA.
Springer
Mitchell G
MG
Fisher
Alfred L
AL
D000818:Animals; D030801:Animals, Genetically Modified; D001151:Arsenic / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D015262:Xenobiotics / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015262:Xenobiotics; C544165:aip-1 protein, C elegans; C073702:skn-1 protein, C elegans; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex; D001151:Arsenic