The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution

Schmitt-Ney, Michel

doi:10.3390/cells9030787

Cited by 38 publications

(27 citation statements)

References 135 publications

(144 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FOX is evolutionarily conserved in eukaryotic organisms and a crucial regulator of embryonic development, which is affected by hormone signaling [ 33 , 34 ]. In contrast to the highly conserved FOX domain, forkhead TF proteins are highly divergent in other parts of their sequences [ 35 ]. In humans, forkhead TFs modulate signaling pathways [ 36 ], and can be a direct target of hormonal medications such as progestin to inhibit epithelial cell growth [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance

et al. 2021

View full text Add to dashboard Cite

Background Pre-harvest sprouting (PHS) in wheat can cause severe damage to both grain yield and quality. Resistance to PHS is a quantitative trait controlled by many genes located across all 21 wheat chromosomes. The study targeted a large-effect quantitative trait locus (QTL) QPhs.ccsu-3A.1 for PHS resistance using several sets previously developed near-isogenic lines (NILs). Two pairs of NILs with highly significant phenotypic differences between the isolines were examined by RNA sequencing for their transcriptomic profiles on developing seeds at 15, 25 and 35 days after pollination (DAP) to identify candidate genes underlying the QTL and elucidate gene effects on PHS resistance. At each DAP, differentially expressed genes (DEGs) between the isolines were investigated. Results Gene ontology and KEGG pathway enrichment analyses of key DEGs suggested that six candidate genes underlie QPhs.ccsu-3A.1 responsible for PHS resistance in wheat. Candidate gene expression was further validated by quantitative RT-PCR. Within the targeted QTL interval, 16 genetic variants including five single nucleotide polymorphisms (SNPs) and 11 indels showed consistent polymorphism between resistant and susceptible isolines. Conclusions The targeted QTL is confirmed to harbor core genes related to hormone signaling pathways that can be exploited as a key genomic region for marker-assisted selection. The candidate genes and SNP/indel markers detected in this study are valuable resources for understanding the mechanism of PHS resistance and for marker-assisted breeding of the trait in wheat.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Foxo is encoded by single genes in C. elegans and Drosophila, but in mammals comprises a family of related factors encoded by distinct genes. Foxo family members tend to be co-expressed within cells and exhibit functional redundancy 14 , although discrete roles of specific family members are sometimes observed 15 . The effects of Foxo activity, which are growth inhibition, tumor suppression, and stress resistance 16 , tend to be similar to those of AMPK but opposite to those of Tor.…”

Section: Similar Signaling Pathway Disruptions Are Observed In Neurodegenerative and Muscle Degenerative Disordersmentioning

confidence: 99%

A transition to degeneration triggered by oxidative stress in degenerative disorders

Stern

McNew

2020

Mol Psychiatry

View full text Add to dashboard Cite

Although the activities of many signaling pathways are dysregulated during the progression of neurodegenerative and muscle degeneration disorders, the precise sequence of cellular events leading to degeneration have not been fully elucidated. Two kinases of particular interest, the growth-promoting Tor kinase and the energy sensor AMPK, appear to show reciprocal changes in activity during degeneration, with increased Tor activity and decreased AMPK activity reported. These changes in activity have been predicted to cause degeneration by attenuating autophagy, leading to accumulation of unfolded protein aggregates and dysfunctional mitochondria, the consequent increased production of reactive oxygen species (ROS), and ultimately oxidative damage. Here we propose that this increased ROS production not only causes oxidative damage but also ultimately induces an oxidative stress response that reactivates the redox-sensitive AMPK and activates the redox-sensitive stress kinase JNK. Activation of these kinases re-activates autophagy. Because at this late stage, cells have become filled with dysfunctional mitochondria and protein aggregates, which are autophagy targets, this autophagy reactivation induces degeneration. The mechanism proposed here emphasizes that the process of degeneration is dynamic, that dysregulated signaling pathways change over time and can transition from deleterious to beneficial and vice versa as degeneration progresses.

show abstract

“…FOXO3a belongs to the FOXO subfamily of forkhead transcription factors. In human, the FOXO transcription factors are encoded by five genes, including FOXO1, FOXO3a, FOXO3b, FOXO4, and FOXO6 [10]. In the context of cancer, the physiological function of FoxO3a is to stimulate some cellular mechanism including proliferation, apoptosis, DNA damage, the activation of reactive oxygen species, cell cycle progression, and tumorigenesis [11], [12].…”

Section: Introductionmentioning

confidence: 99%

The Levels of FoxO3a Predict the Failure of Imatinib Mesylate Therapy among Chronic Myeloid Leukemia Patients

Wardhani

Susanti

Rahayu

et al. 2021

Open Access Maced J Med Sci

View full text Add to dashboard Cite

INTRODUCTION: Forkhead Transcription Factor 3a (FoxO3a) has been proposed to have a high efficacy to predict the failure of imatinib mesylate (IM) therapy among Chronic Myeloid Leukemia (CML) patients. However, the limited evidence had made this marker remained controversy. OBJECTIVES: We aimed to investigate the correlation between the levels of FoxO3a and the risk of treatment failure of IM therapy in CML patients. METHODS: A prospective cohort study was carried out between February 2019 and February 2020 in Saiful Anwar Hospital, Malang, Indonesia. All CML patients treated with IM on our hospital during the study period were included. The levels of FoxO3a was determined using the Enzyme-linked immunosorbent assay (ELISA) using Cusabio Biotech Kit (Cusabio Biotech Co., New York, USA). The treatment response was assessed using the European Leukemia criteria. The correlation and effect estimate between the levels of FoxO3a and treatment response of CML patients was assessed using multiple logistic regression. RESULTS: 53 CML patients receiving IM in our hospital were included, consisting of 29 patients with good response and 24 patients with non-response. Our study found that CML patients with lower levels of FoxO3a was associated with increased risk to develop treatment failure when treated with IM. Moreover, we also found that higher risk of treatment failure of IM therapy was also found in patients with increased levels of thrombocytes, basophils, and leukocytes, and lower levels of hemoglobin. CONCLUSION: We reveal that FoxO3a is the prominent marker to predict the treatment response of CML patients treated with IM.

show abstract

The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution

Cited by 38 publications

References 135 publications

Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance

Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance

A transition to degeneration triggered by oxidative stress in degenerative disorders

The Levels of FoxO3a Predict the Failure of Imatinib Mesylate Therapy among Chronic Myeloid Leukemia Patients

Contact Info

Product

Resources

About