Forkhead box o as a sensor, mediator, and regulator of redox signaling.

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.

journal_name

Antioxid Redox Signal

authors

de Keizer PL,Burgering BM,Dansen TB

doi

10.1089/ars.2010.3403

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

1093-106

issue

6

eissn

1523-0864

issn

1557-7716

journal_volume

14

pub_type

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