Chapter

Forkhead Transcription Factors

Volume 665 of the series Advances in Experimental Medicine and Biology pp 242-260

The “O” Class: Crafting Clinical Care with FoxO Transcription Factors

  • Kenneth MaieseAffiliated withDivision of Cellular and Molecular Cerebral Ischemia, Wayne State University School of MedicineDepartment of Neurology, Wayne State University School of MedicineDepartment of Anatomy and Cell Biology, Wayne State University School of MedicineBarbara Ann Karmanos Cancer Institute, Wayne State University School of MedicineCenter for Molecular Medicine and Genetics, Wayne State University School of MedicineInstitute of Environmental Health Sciences, Wayne State University School of Medicine Email author 
  • , Zhao Zhong ChongAffiliated withDivision of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine
  • , Jinling HouAffiliated withDivision of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine
  • , Yan Chen ShangAffiliated withDivision of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine

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Abstract

Forkhead Transcription Factors: Vital Elementsin 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 and Medicine 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.