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Nuclear/cytoplasmic shuttling of the transcription factor FoxO1 is regulated by neurotrophic factors
Gan L.1; Zheng W.1; Chabot J.-G.1; Unterman T.G.2; Quirion R.1
2005-06-01
Source PublicationJournal of Neurochemistry
ISSN00223042
Volume93Issue:5Pages:1209-1219
AbstractFoxO1, a member of the FoxO subfamily of forkhead transcription factors, is an important target for insulin and growth factor signaling in the regulation of metabolism, cell cycle and proliferation, and survival in peripheral tissues. However, its role in the central nervous system is mostly unknown. In this study, we examined the effect of neurotrophic factors on nuclear/cytoplasmic shuttling of FoxO1. We showed that insulin-like growth factor-1 (IGF-1) and nerve growth factor (NGF) potently induced the nuclear exclusion of FoxO1-green fluorescent protein (GFP) while neurotrophin (NT)-3 and NT-4 were much weaker and brain-derived neurotrophic factor (BDNF) failed to induce FoxO1 translocation in PC12 cells. FoxO1 translocation was inhibited by LY294002, a well-established PI3K/Akt kinase inhibitor. Moreover, FoxO1 was phosphorylated at Thr24 and Ser256 residues by the above neurotrophic factors, with the exception of BDNF. Triple mutant FoxO1, in which three Akt/PKB phosphorylation sites (Thr24, Ser256 and Ser319) were mutated to alanine, resulted in the complete nuclear targeting of the expressed FoxO1-GFP fusion protein in the presence of the above neurotrophic factors in both PC12 cells and cultured hippocampal and cortical neurons. Taken together, these findings demonstrate that neurotrophic factors are able to regulate nuclear/cytoplasmic shuttling of FoxO1 via the PI3K/Akt pathway in neuronal cells. © 2005 International Society for Neurochemistry.
KeywordFoxO1 Insulin-like growth factor-1 Nerve growth factor Neurotrophins PC12 cells Trafficking
DOI10.1111/j.1471-4159.2005.03108.x
URLView the original
Language英語
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Cited Times [WOS]:36   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Douglas Hospital Research Center
2.University of Illinois College of Medicine
3.VA Medical Center
Recommended Citation
GB/T 7714
Gan L.,Zheng W.,Chabot J.-G.,et al. Nuclear/cytoplasmic shuttling of the transcription factor FoxO1 is regulated by neurotrophic factors[J]. Journal of Neurochemistry,2005,93(5):1209-1219.
APA Gan L.,Zheng W.,Chabot J.-G.,Unterman T.G.,&Quirion R..(2005).Nuclear/cytoplasmic shuttling of the transcription factor FoxO1 is regulated by neurotrophic factors.Journal of Neurochemistry,93(5),1209-1219.
MLA Gan L.,et al."Nuclear/cytoplasmic shuttling of the transcription factor FoxO1 is regulated by neurotrophic factors".Journal of Neurochemistry 93.5(2005):1209-1219.
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