Department of Neurology and Anatomy and Cell Biology, Barbara Ann Karmanos Cancer Institute, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA.
Adv Exp Med Biol. 2009;665:242-60. doi: 10.1007/978-1-4419-1599-3_18.
Forkhead Transcription Factors: Vital Elements in Biology and Medicine provides a unique platform for the presentation of novel work and new insights into the vital role that forkhead transcription factors play in both cellular physiology as well as clinical medicine. Internationally recognized investigators provide their insights and perspectives for a number of forkhead genes and proteins that may have the greatest impact for the development of new strategies for a broad array of disorders that can involve aging, cancer, cardiac function, neurovascular integrity, fertility, stem cell differentiation, cellular metabolism, and immune system regulation. Yet, the work clearly sets a precedent for the necessity to understand the cellular and molecular function of forkhead proteins since this family of transcription factors can limit as well as foster disease progression depending upon the cellular environment. With this in mind, our concluding chapter for Forkhead Transcription Factors: Vital Elements in Biology andMedicine offers to highlight both the diversity and complexity of the forkhead transcription family by focusing upon the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4, and FoxO6. FoxO proteins are increasingly considered to represent unique cellular targets that can control numerous processes such as angiogenesis, cardiovascular development, vascular tone, oxidative stress, stem cell proliferation, fertility, and immune surveillance. Furthermore, FoxO transcription factors are exciting considerations for disorders such as cancer in light of their pro-apoptotic and inhibitory cell cycle effects as well as diabetes mellitus given the close association FoxOs hold with cellular metabolism. In addition, these transcription factors are closely integrated with several novel signal transduction pathways, such as erythropoietin and Wnt proteins, that may influence the ability of FoxOs to lead to cell survival or cell injury. Further understanding of both the function and intricate nature of the forkhead transcription factor family, and in particular the FoxO proteins, should allow selective regulation of cellular development or cellular demise for the generation of successful future clinical strategies and patient well-being.
生物学和医学中的重要元素为呈现叉头转录因子在细胞生理学和临床医学中的重要作用的新工作和新见解提供了一个独特的平台。国际知名研究人员为许多叉头基因和蛋白质提供了他们的见解和观点，这些基因和蛋白质可能对广泛涉及衰老、癌症、心脏功能、神经血管完整性、生育、干细胞分化、细胞代谢和免疫系统调节的多种疾病的新策略的发展产生最大影响。然而，这项工作显然为理解叉头蛋白的细胞和分子功能设定了一个先例，因为这个转录因子家族可以根据细胞环境限制和促进疾病进展。考虑到这一点，我们的《生物学和医学中的叉头转录因子：重要元素》一书的最后一章提供了一个亮点，即通过关注哺乳动物 O 类叉头转录因子（FoxO）中的 FoxO1、FoxO3、FoxO4 和 FoxO6，强调叉头转录家族的多样性和复杂性。FoxO 蛋白越来越被认为是代表独特的细胞靶标，可以控制许多过程，如血管生成、心血管发育、血管张力、氧化应激、干细胞增殖、生育和免疫监视。此外，鉴于 FoxO 与细胞代谢的密切关联，FoxO 转录因子在癌症等疾病中被认为是令人兴奋的考虑因素，因为它们具有促凋亡和抑制细胞周期的作用，以及糖尿病。此外，这些转录因子与几种新型信号转导途径密切相关，如促红细胞生成素和 Wnt 蛋白，这可能影响 FoxO 导致细胞存活或细胞损伤的能力。进一步了解叉头转录因子家族的功能和复杂性质，特别是 FoxO 蛋白，应该允许选择性调节细胞发育或细胞死亡，以制定成功的未来临床策略和提高患者的健康水平。
