skn-1-dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans

Annabel A. Ferguson, Mitchell G. Springer, Alfred L Fisher

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 Aβ 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.

Original languageEnglish (US)
Pages (from-to)2651-2667
Number of pages17
JournalMolecular and Cellular Biology
Volume30
Issue number11
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Fingerprint

Physiological Stress
Caenorhabditis elegans
Proteins
Arsenic
Proteome
RNA Interference
Genes
Tyrosine
Shock
Oxidative Stress
Transcription Factors
Hot Temperature
Maintenance

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

skn-1-dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans. / Ferguson, Annabel A.; Springer, Mitchell G.; Fisher, Alfred L.

In: Molecular and Cellular Biology, Vol. 30, No. 11, 01.06.2010, p. 2651-2667.

Research output: Contribution to journalArticle

@article{9e92f746a8f94982bc8520f7e2ad5e76,
title = "skn-1-dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans",
abstract = "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 Aβ 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.",
author = "Ferguson, {Annabel A.} and Springer, {Mitchell G.} and Fisher, {Alfred L}",
year = "2010",
month = "6",
day = "1",
doi = "10.1128/MCB.01340-09",
language = "English (US)",
volume = "30",
pages = "2651--2667",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - skn-1-dependent and -independent regulation of aip-1 expression following metabolic stress in Caenorhabditis elegans

AU - Ferguson, Annabel A.

AU - Springer, Mitchell G.

AU - Fisher, Alfred L

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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 Aβ 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.

AB - 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 Aβ 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.

UR - http://www.scopus.com/inward/record.url?scp=77952647809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952647809&partnerID=8YFLogxK

U2 - 10.1128/MCB.01340-09

DO - 10.1128/MCB.01340-09

M3 - Article

VL - 30

SP - 2651

EP - 2667

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 11

ER -