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Introduction to FOXO Biology

Review · human · Methods in molecular biology (Clifton, N.J.) · 2019 · DOI 10.1007/978-1-4939-8900-3_1 · PMID 30414140

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This review introduces the biology of Forkhead box O (FOXO) transcription factors, describing four family members in mammals — FOXO1, FOXO3a, FOXO4, and FOXO6 — originally identified as downstream regulators of the insulin pathway. It describes FOXO factors as binding promoters of diverse target genes and controlling processes including cellular energy production, oxidative stress resistance, and cell viability and proliferation. The review states that deregulation of FOXO proteins has been shown to play a role in metabolic disorders, human longevity, and tumor suppression, and notes that because FOXO activity is controlled by posttranslational modifications, inactivation of FOXOs mostly occurs through overactivation of upstream modifying enzymes, which the review describes as providing possibilities for restoring FOXO activity pharmaceutically.

Abstract

Forkhead box O (FOXO) proteins are a family of transcription factors with four members in mammals, namely FOXO1, FOXO3a, FOXO4, and FOXO6. FOXO factors, originally identified as downstream regulators of the insulin pathway, are known to bind to the promoters of a broad variety of target genes and control several processes of key importance for cellular homeostasis including cellular energy production, oxidative stress resistance, and cell viability and proliferation. Accordingly, deregulation of FOXO proteins has been shown to play an essential role in metabolic disorders, human longevity, and the suppression of tumors. As the activity of these transcription factors is controlled by posttranslational modifications, inactivation of FOXOs occurs mostly due to the overactivation of their upstream modifying enzymes providing a wealth of possibilities for restoring FOXO activity pharmaceutically.

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