E2F Transcription Factor 1 Regulates Cellular and Organismal Senescence by Inhibiting Forkhead Box O Transcription Factors

Xie, Qi; Shan, Peng; Li, Tao; Ruan, Haihe; Yang, Yanglu; Li, Tie-Mei; Adams, Ursula; Shao, Meng; Bi, Xiaolin; Dong, Meng‐Qiu; Yuan, Zengqiang

doi:10.1074/jbc.m114.587170

Cited by 39 publications

(30 citation statements)

References 34 publications

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“…16g). Moreover, the same result was later reported by another group in connection with daf-16 regulation, both in C. elegans and in a mammalian system (Xie et al 2014 We have already given an overview and provided some data on transcription factors with the main function during development that have a large effect on lifespan when downregulated or upregulated post developmentally. One more such transcription factor, ceh-22/F29F11.5, has been studied in connection with hlh-2/M05B5.5 and fits the same paradigm of the developmental theory of aging.…”

supporting

confidence: 78%

Identification and characterization of inter-species aging-related transcriptomic regulators

Rozanov

Mansfeld

Zarse

et al. 2017

Free Radical Biology and Medicine

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supporting

confidence: 78%

Identification and characterization of inter-species aging-related transcriptomic regulators

Rozanov

Mansfeld

Zarse

et al. 2017

Free Radical Biology and Medicine

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“…Conserved targets also exhibited enrichment for E2F, bZIP, and NFY motifs. Interestingly, E2F regulates cellular senescence in mammalian cells, and E2F ( efl‐1 ) knockout in C. elegans extends lifespan in a daf‐16 ‐dependent manner (Xie et al ., ). Intriguingly, the bZIP family of transcription factors includes CREB, which has been implicated in lifespan regulation and loss of learning and memory with age in worms (Kauffman et al ., ; Mair et al ., ).…”

Section: Resultsmentioning

confidence: 97%

Characterization of the direct targets ofFOXOtranscription factors throughout evolution

Webb

Kundaje

Brunet³

2016

Aging Cell

169

159

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Summary FOXO transcription factors (FOXOs) are central regulators of lifespan across species, yet they also have cell‐specific functions, including adult stem cell homeostasis and immune function. Direct targets of FOXOs have been identified genome‐wide in several species and cell types. However, whether FOXO targets are specific to cell types and species or conserved across cell types and throughout evolution remains uncharacterized. Here, we perform a meta‐analysis of direct FOXO targets across tissues and organisms, using data from mammals as well as Caenorhabditis elegans and Drosophila. We show that FOXOs bind cell type‐specific targets, which have functions related to that particular cell. Interestingly, FOXOs also share targets across different tissues in mammals, and the function and even the identity of these shared mammalian targets are conserved in invertebrates. Evolutionarily conserved targets show enrichment for growth factor signaling, metabolism, stress resistance, and proteostasis, suggesting an ancestral, conserved role in the regulation of these processes. We also identify candidate cofactors at conserved FOXO targets that change in expression with age, including CREB and ETS family factors. This meta‐analysis provides insight into the evolution of the FOXO network and highlights downstream genes and cofactors that may be particularly important for FOXO's conserved function in adult homeostasis and longevity.

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“…In human fibroblasts, E2F-1 enhances cellular senescence, whereas FoxOs antagonize senescence by upregulating the formation of ROS scavenging proteins [154,155] . Xie et al [156] showed that E2F-1 attenuates FoxO3a-mediated expression of MnSOD and catalase. They mapped interaction between E2F-1 and FoxO3a to a region including the DNA binding domain of E2F-1 and the C-terminal transcription activation domain of FoxO3a.…”

Section: Redox Regulation Of Foxo Expressionmentioning

confidence: 99%

“…They mapped interaction between E2F-1 and FoxO3a to a region including the DNA binding domain of E2F-1 and the C-terminal transcription activation domain of FoxO3a. They propose that E2F-1 inhibits FoxO3a function by directly binding FoxO3a in the nucleus and preventing the activation of its target genes [156] . Depending on the cellular and promoter context (and possibly also on the redox conditions in the cell), the two proteins can therefore act synergistically, or one can antagonize the activity of the other.…”

Section: Redox Regulation Of Foxo Expressionmentioning

confidence: 99%

Redox regulation of FoxO transcription factors

et al. 2015

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Transcription factors of the forkhead box, class O (FoxO) family are important regulators of the cellular stress response and promote the cellular antioxidant defense. On one hand, FoxOs stimulate the transcription of genes coding for antioxidant proteins located in different subcellular compartments, such as in mitochondria (i.e. superoxide dismutase-2, peroxiredoxins 3 and 5) and peroxisomes (catalase), as well as for antioxidant proteins found extracellularly in plasma (e.g., selenoprotein P and ceruloplasmin). On the other hand, reactive oxygen species (ROS) as well as other stressful stimuli that elicit the formation of ROS, may modulate FoxO activity at multiple levels, including posttranslational modifications of FoxOs (such as phosphorylation and acetylation), interaction with coregulators, alterations in FoxO subcellular localization, protein synthesis and stability. Moreover, transcriptional and posttranscriptional control of the expression of genes coding for FoxOs is sensitive to ROS. Here, we review these aspects of FoxO biology focusing on redox regulation of FoxO signaling, and with emphasis on the interplay between ROS and FoxOs under various physiological and pathophysiological conditions. Of particular interest are the dual role played by FoxOs in cancer development and their key role in whole body nutrient homeostasis, modulating metabolic adaptations and/or disturbances in response to low vs. high nutrient intake. Examples discussed here include calorie restriction and starvation as well as adipogenesis, obesity and type 2 diabetes.

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E2F Transcription Factor 1 Regulates Cellular and Organismal Senescence by Inhibiting Forkhead Box O Transcription Factors

Cited by 39 publications

References 34 publications

Identification and characterization of inter-species aging-related transcriptomic regulators

Identification and characterization of inter-species aging-related transcriptomic regulators

Characterization of the direct targets ofFOXOtranscription factors throughout evolution

Redox regulation of FoxO transcription factors

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