FOXOs: masters of the equilibrium.
FOXOs: masters of the equilibrium.
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DOI：
10.1111/febs.16221
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发表时间：
2022-12
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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叉头框0（FOXO）转录因子（TF）是叉头TF大家族的一个亚类。哺乳动物表达FOXO 1、FOXO 3、FOXO 4和FOXO 6四种成员。对FOXO功能的兴趣主要源于它们在确定寿命方面的观察到的作用，其中在模式生物中，FOXO活性增加导致寿命延长。FOXO作为几种信号通路的下游，通过翻译后修饰广泛调节。FOXO在各种细胞类型、生物体和各种条件下激活的转录程序已被描述，并对介导FOXO功能的关键转录靶点有了一些了解。在细胞水平上，这些研究揭示了FOXO在细胞代谢、细胞氧化还原、细胞增殖、DNA修复、自噬等方面的作用。这里出现的一般情况是FOXO起着保持平衡的作用，它们对细胞内稳态很重要。在这里，我们将首先简要总结FOXO调节的一般知识和可能的功能。我们将使用基因组稳定性来说明FOXO如何确保体内平衡。基因组稳定性对于保持遗传完整性至关重要，因此可以预防疾病。然而，基因组突变需要在一生中发生才能进化，但它们的积累被认为是衰老的原因。因此，FOXO在基因组稳定性中的作用可能是其在寿命和衰老中的作用的基础。最后，我们将提出一些关于FOXO功能的未知问题，我们相信这些问题的答案将进一步加深我们对FOXO功能的理解，并最终有助于理解寿命及其后果。细胞外和细胞内环境的变化导致“细胞应激”，这是潜在的有害因素，可以迫使平衡从健康转变为患病，最终导致生物体死亡。叉头盒O（FOXO）转录因子是平衡的调节剂，并确保最佳的细胞功能和寿命。有四种FOXO亚型，因此，这里要解决的问题是：FOXO是作为一个家族还是以亚型特异性的方式保持平衡？
Forkhead box O (FOXO) transcription factors (TFs) are a subclass of the larger family of forkhead TFs. Mammalians express four members FOXO1, FOXO3, FOXO4, and FOXO6. The interest in FOXO function stems mostly from their observed role in determining lifespan, where in model organisms, increased FOXO activity results in extended lifespan. FOXOs act as downstream of several signaling pathway and are extensively regulated through post‐translational modifications. The transcriptional program activated by FOXOs in various cell types, organisms, and under various conditions has been described and has shed some light on what the critical transcriptional targets are in mediating FOXO function. At the cellular level, these studies have revealed a role for FOXOs in cell metabolism, cellular redox, cell proliferation, DNA repair, autophagy, and many more. The general picture that emerges hereof is that FOXOs act to preserve equilibrium, and they are important for cellular homeostasis. Here, we will first briefly summarize the general knowledge of FOXO regulation and possible functions. We will use genomic stability to illustrate how FOXOs ensure homeostasis. Genomic stability is critical for maintaining genetic integrity, and therefore preventing disease. However, genomic mutations need to occur during lifetime to enable evolution, yet their accumulation is believed to be causative to aging. Therefore, the role of FOXO in genomic stability may underlie its role in lifespan and aging. Finally, we will come up with questions on some of the unknowns in FOXO function, the answer(s) to which we believe will further our understanding of FOXO function and ultimately may help to understand lifespan and its consequences. Changes in the extracellular and intracellular environment cause ‘cellular stress’ that is potentially detrimental and can force an equilibrium shift from healthy to diseased and eventually organismal death. Forkhead box O (FOXO) transcription factors are regulators of the equilibrium and ensure optimal cellular function and lifespan. There are four FOXO isoforms, and hence, the question addressed here: Do FOXOs act to preserve the equilibrium as a family or in an isoform‐specific manner?
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
3.5
作者：
Bourgeois B;Madl T
通讯作者：
Madl T
影响因子：
14.9
作者：
Bianco JN;Schumacher B
通讯作者：
Schumacher B
DOI：
10.18632/aging.100471
发表时间：
2012-07
期刊：
Aging
影响因子：
--
作者：
Calnan DR;Webb AE;White JL;Stowe TR;Goswami T;Shi X;Espejo A;Bedford MT;Gozani O;Gygi SP;Brunet A
通讯作者：
Brunet A