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Journal of Biochemistry 2007 141(6):769-774; doi:10.1093/jb/mvm104
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© 2007 The Japanese Biochemical Society.

JB Minireviews-Genome Decoding Systems

FOXO Transcription Factors in the Regulatory Networks of Longevity

Hiroaki Daitoku and Akiyoshi Fukamizu*

Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

*To whom correspondence should be addressed. Tel/Fax: +81-29-853-6070, E-mail: akif{at}tara.tsukuba.ac.jp

Received October 2, 2006; Accepted November 1, 2006


  Abstract

FOXO (Forkhead box O) transcription factors constitute an evolutionally conserved subgroup within the large Forkhead family of transcription regulators. FOXO factors are important regulators of the cell cycle, apoptosis, DNA repair, metabolism, oxidative stress resistance and longevity. Genetic studies of Caenorhabditis elegans demonstrated that FOXO factors are major targets of the insulin-like signalling implicated during the regulation of glucose metabolism and lifespan extension. Recently, emerging evidence has also shed light on signalling pathways under oxidative stress that regulate FOXO activity by various post-translational modifications, including phosphorylation, acetylation and ubiquitination. Thus, FOXO factors react to external stimuli by altering their modifications, modulating target gene expression that may be involved in longevity.

Key Words: FOXO, lifespan regulation, oxidative stress, post-translational modification, transcription


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