The purpose of the current study was to determine whether heat shock protein 70 (Hsp70) directly regulates forkhead box O (FOXO) signaling in skeletal muscle. This aim stems from previous work demonstrating that Hsp70 overexpression inhibits disuse-induced FOXO transactivation and prevents muscle fiber atrophy. However, although FOXO is sufficient to cause muscle wasting, no data currently exis...

The forkhead boxO transcription factor (FOXO) is a component of the insulin signalling pathway and plays a role in responding to adverse conditions, such as oxidative stress and starvation. In stressful conditions, FOXO moves from the cytosol to the nucleus where it activates gene expression programmes. Here, we show that FOXO in Drosophila melanogaster responds to heat stress as it does to oth...

The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known as 'forkhead box' domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senesc...

We investigated whether insulin signaling, known to mediate physiological plasticity in response to changes in nutrition, also facilitates discrete phenotypic responses such as polyphenisms. We test the hypothesis that the gene FOXO--which regulates growth arrest under nutrient stress--mediates a nutritional polyphenism in the horned beetle, Onthophagus nigriventris. Male beetles in the genus O...

Studies in simple model organisms have yielded crucial insights into the genetic and molecular aspects of longevity. FOXO, which is most notable for its association with longevity, and its upstream regulators such as sirtuins have received particular attention in translational research because these genes modulate cell survival in several models of neurodegenerative diseases. There is a large a...

The PI3K/AKT signaling pathway contributes to cell cycle progression of cytokine-dependent hematopoietic cells under normal conditions, and it is absolutely required to override DNA damage-induced cell cycle arrest checkpoints in these cells. Phosphatidylinositol-3-kinase (PI3K)/AKT activity also correlates with Cdk2 activity in hematopoietic cells, suggesting that Cdk2 activation may be a rele...

Forkhead transcription factors of the FOXO family are important downstream targets of protein kinase B (PKB)/Akt, a kinase shown to play a decisive role in cell proliferation and cell survival. Direct phosphorylation by PKB/Akt inhibits transcriptional activation by FOXO factors, causing their displacement from the nucleus into the cytoplasm. Work from recent years has shown that this family of...

Keratinocyte stress-response of the uninvolved psoriatic epidermis is known to be altered compared healthy cells. Therefore, we aimed reveal potential mechanisms underlying this alteration. We expression annotated cell-stress-related proteins between and skin using protein array method. Data were analyzed by Reactome over-representation test. found that p27/CDKN1B cytochrome C showed at least a...

Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within ...

The FoxO forkhead transcription factors FoxO4 (AFX), FoxO3a (FKHR.L1), and FoxO1a (FKHR) represent important physiological targets of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB) signaling. Overexpression or conditional activation of FoxO factors is able to antagonize many responses to constitutive PI3K/PKB activation including its effect on cellular proliferation. It was previou...