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Forkhead box o as a sensor, mediator, and regulator of redox signaling.
MedLine Citation:
PMID:  20626320     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract The forkhead box O (FOXO) family of transcription factors regulates a variety of cellular programs, including cell cycle arrest, reactive oxygen species (ROS) scavenging, and apoptosis, and are of key importance in the decision over cell fate. In animal model systems it has been shown that FOXO is involved in the regulation of long lifespan. FOXO activity is tightly controlled by the insulin signaling pathway and by a multitude of ROS-induced posttranslational modifications. In the cell, ROS levels can be sensed by virtue of stimulatory and inhibitory oxidative modification of cysteine residues within proteins that control various signaling cascades. Recently, it was shown that cysteines in FOXO can also act as sensors of the local redox state. In this review we have outlined the cysteine-dependent redox switches that regulate both the insulin and ROS signaling pathways upstream of FOXO. Further, we describe how FOXO controls ROS levels by transcriptional regulation of a multilayered antioxidant system. Finally, we will discuss how cysteine-based redox signaling to FOXO could play a role in fine-tuning the optimal cellular response to ROS to control organismal lifespan. Antioxid. Redox Signal. 14, 1093-1106.
Authors:
Peter L J de Keizer; Boudewijn M T Burgering; Tobias B Dansen
Publication Detail:
Type:  Journal Article     Date:  2010-09-20
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  14     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1093-106     Citation Subset:  IM    
Affiliation:
Department of Physiological Chemistry, Centre for Biomedical Genetics and Cancer Genomics Centre, University Medical Center Utrecht , Utrecht, The Netherlands .
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