Integrating opposing signals toward Forkhead box O

Antioxidants & Redox Signaling
Maaike C W van den Berg, Boudewijn M T Burgering

Abstract

Transcription factors are the common convergence points of signal transduction pathways to affect gene transcription. Signal transduction activity results in posttranslational modification (PTM) of transcription factors and the sum of these modifications at any given time point will determine the action of the transcription factor. It has been suggested that these PTMs provide a transcription factor code analogous to the histone code. However, the number and variety of these modifications and the lack of knowledge in general of their dynamics precludes at present a concise view of how combinations of PTMs affect transcription factor function. Also, a single type of PTM such as phosphorylation can have opposing effects on transcription factor activity. Transcription factors of the Forkhead box O (FOXO) class are predominantly regulated through signaling, by phosphoinositide 3-kinase/protein kinase B (also known as AKT) pathway and a reactive oxygen species/c-Jun N-terminal kinase pathway. Both pathways result in increased FOXO phosphorylation yet with opposing result. Whereas PKB-mediated phosphorylation inactivates FOXO, c-Jun N-terminal kinase-mediated phosphorylation results in activation of FOXO. Here we discuss regulation o...Continue Reading

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Citations

Sep 3, 2011·Cell Stem Cell·Kevin Andrew Uy Gonzales, Huck-Hui Ng
Aug 2, 2011·Nature Cell Biology·Xin ZhangSaghi Ghaffari
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Jan 18, 2011·Antioxidants & Redox Signaling·Anna A Szypowska, Boudewijn M T Burgering
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May 21, 2015·The Biochemical Journal·David E A KloetBoudewijn M T Burgering

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Methods Mentioned

BETA
nuclear translocation
ubiquitination
acetylation
GTPase

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