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Tissue-Specific Metabolic Regulation of FOXO-Binding Protein: FOXO Does Not Act Alone
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The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution

Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126 Torino, Italy
Cells 2020, 9(3), 787; https://doi.org/10.3390/cells9030787
Received: 1 February 2020 / Revised: 16 March 2020 / Accepted: 23 March 2020 / Published: 24 March 2020
(This article belongs to the Special Issue The FoxO Transcription Factors and Metabolic Regulation)
The nematode Caenorhabditis elegans possesses a unique (with various isoforms) FOXO transcription factor DAF-16, which is notorious for its role in aging and its regulation by the insulin-PI3K-AKT pathway. In humans, five genes (including a protein-coding pseudogene) encode for FOXO transcription factors that are targeted by the PI3K-AKT axis, such as in C. elegans. This common regulation and highly conserved DNA-binding domain are the pillars of this family. In this review, I will discuss the possible meaning of possessing a group of very similar proteins and how it can generate additional functionality to more complex organisms. I frame this discussion in relation to the much larger super family of Forkhead proteins to which they belong. FOXO members are very often co-expressed in the same cell type. The overlap of function and expression creates a certain redundancy that might be a safeguard against the accidental loss of FOXO function, which could otherwise lead to disease, particularly, cancer. This is one of the points that will be examined in this “family affair” report. View Full-Text
Keywords: FOXO; transcription; gene family; PI3K; AKT; insulin pathway; tumor suppressor; cancer; aging; gene duplication; genetic redundancy; evolution; FOX; forkhead; metabolism FOXO; transcription; gene family; PI3K; AKT; insulin pathway; tumor suppressor; cancer; aging; gene duplication; genetic redundancy; evolution; FOX; forkhead; metabolism
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Schmitt-Ney, M. The FOXO’s Advantages of Being a Family: Considerations on Function and Evolution. Cells 2020, 9, 787.

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