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Review
. 2013 Dec 31;1(1):e5.
doi: 10.15190/d.2013.5.

Critical physiological and pathological functions of Forkhead Box O tumor suppressors

Georgiana R Dumitrascu  1 , Octavian Bucur  2
Affiliations
Review

Critical physiological and pathological functions of Forkhead Box O tumor suppressors

Georgiana R Dumitrascu et al. Discoveries (Craiova). .

Abstract

The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases.

Keywords: FOX; FOXO; FOXO1; FOXO3; apoptosis; cancer; cancer stem cells; cell cycle; differentiation; metabolism; microRNAs; small non-coding RNAs; stem cells.

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Conflict of interest statement

Conflict of interests: There are no conflicts of interest.

Figures

Figure 1
Figure 1. Structure of FOXO family members
FOXO1 and FOXO3 are exemplified here. In humans, the primary structure of the FOXO proteins is characterized by a length of approximately 655-675 amino acid residues (aa) for FOXO1 (655 aa) and FOXO3 (673 aa), while FOXO4 has 505 aa and FOXO6 492 aa All members of the FOXO family consist of four domains: a forkhead DNA-binding domain (DBD), a nuclear localization signal (NLS), a nuclear export sequence (NES) and a C-terminal transactivation domain.
Figure 2
Figure 2. Functions of FOXO family of transcription factors
FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance.
Figure 3
Figure 3. Selective list of FOXO regulated transcriptional targets
See this image and copyright information in PMC

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