Linked Life Data

17714076

Source:http://linkedlifedata.com/resource/pubmed/id/17714076

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-7
pubmed:abstractText
SKN-1 in the nematode worm Caenorhabditis elegans is functionally orthologous to mammalian NRF2 [NF-E2 (nuclear factor-E2)-related factor 2], a protein regulating response to oxidative stress. We have examined both the expression and activity of SKN-1 in response to a variety of oxidative stressors and to down-regulation of specific gene targets by RNAi (RNA interference). We used an SKN-1-GFP (green fluorescent protein) translational fusion to record changes in both skn-1 expression and SKN-1 nuclear localization, and a gst-4-GFP transcriptional fusion to measure SKN-1 transcriptional activity. GST-4 (glutathione transferase-4) is involved in the Phase II oxidative stress response and its expression is lost in an skn-1(zu67) mutant. In the present study, we show that the regulation of skn-1 is tied to the protein-degradation machinery of the cell. RNAi-targeted removal of most proteasome subunits in C. elegans caused nuclear localization of SKN-1 and, in some cases, induced transcription of gst-4. Most intriguingly, RNAi knockdown of proteasome core subunits caused nuclear localization of SKN-1 and induced gst-4, whereas RNAi knockdown of proteasome regulatory subunits resulted in nuclear localization of SKN-1 but did not induce gst-4. RNAi knockdown of ubiquitin-specific hydrolases and chaperonin components also caused nuclear localization of SKN-1 and, in some cases, also induced gst-4 transcription. skn-1 activation by proteasome dysfunction could be occurring by one or several mechanisms: (i) the reduced processivity of dysfunctional proteasomes may allow oxidatively damaged by-products to build up, which, in turn, activate the skn-1 stress response; (ii) dysfunctional proteasomes may activate the skn-1 stress response by blocking the constitutive turnover of SKN-1; and (iii) dysfunctional proteasomes may activate an unidentified signalling pathway that feeds back to control the skn-1 stress response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
409
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
205-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in Caenorhabditis elegans.
pubmed:affiliation
Institute for Behavioral Genetics, University of Colorado at Boulder, Box 447, Boulder, CO 80309, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't