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      FoxO1: a novel insight into its molecular mechanisms in the regulation of skeletal muscle differentiation and fiber type specification

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          Abstract

          FoxO1, a member of the forkhead transcription factor forkhead box protein O (FoxO) family, is predominantly expressed in most muscle types. FoxO1 is a key regulator of muscle growth, metabolism, cell proliferation and differentiation. In the past two decades, many researches have indicated that FoxO1 is a negative regulator of skeletal muscle differentiation while contrasting opinions consider that FoxO1 is crucial for myoblast fusion. FoxO1 is expressed much higher in fast twitch fiber enriched muscles than in slow muscles and is also closely related to muscle fiber type specification. In this review, we summarize the molecular mechanisms of FoxO1 in the regulation of skeletal muscle differentiation and fiber type specification.

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          FoxOs at the crossroads of cellular metabolism, differentiation, and transformation.

          Forkhead transcription factors of the FoxO subfamily are emerging as a shared component among pathways regulating diverse cellular functions, such as differentiation, metabolism, proliferation, and survival. Their transcriptional output is controlled via a two-tiered mechanism of phosphorylation and acetylation. Modest alterations of this balance can result in profound effects. The gamut of phenotypes runs from protection against diabetes and predisposition to neoplasia, conferred by FoxO loss of function, to increased cellular survival and a marked catabolic response associated with gain of function.
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            FOXO transcription factors: key regulators of cellular quality control.

            FOXO transcription factors are conserved regulators of longevity downstream of insulin signaling. These transcription factors integrate signals emanating from nutrient deprivation and stress stimuli to coordinate programs of genes involved in cellular metabolism and resistance to oxidative stress. Here, we discuss emerging evidence for a pivotal role of FOXO factors in promoting the expression of genes involved in autophagy and the ubiquitin-proteasome system--two cell clearance processes that are essential for maintaining organelle and protein homeostasis (proteostasis). The ability of FOXO to maintain cellular quality control appears to be critical in processes and pathologies where damaged proteins and organelles accumulate, including aging and neurodegenerative diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis.

              We have studied the role of Notch-1 and its antagonist Numb in the activation of satellite cells during postnatal myogenesis. Activation of Notch-1 promoted the proliferation of myogenic precursor cells expressing the premyoblast marker Pax3. Attenuation of Notch signaling by increases in Numb expression led to the commitment of progenitor cells to the myoblast cell fate and the expression of myogenic regulatory factors, desmin, and Pax7. In many intermediate progenitor cells, Numb was localized asymmetrically in actively dividing cells, suggesting an asymmetric cell division and divergent cell fates of daughter cells. The results indicate that satellite cell activation results in a heterogeneous population of precursor cells with respect to Notch-1 activity and that the balance between Notch-1 and Numb controls cellular homeostasis and cell fate determination.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                7 February 2017
                25 October 2016
                : 8
                : 6
                : 10662-10674
                Affiliations
                1 Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
                Author notes
                Correspondence to: Zhiqing Huang, zqhuang@ 123456sicau.edu.cn
                Article
                12891
                10.18632/oncotarget.12891
                5354690
                27793012
                f0278f86-7b97-4c9f-8eb5-17604f7dc5ca
                Copyright: © 2017 Xu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 September 2016
                : 19 October 2016
                Categories
                Review

                Oncology & Radiotherapy
                foxo1,skeletal muscle,differentiation,fiber type specification,molecular mechanisms

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