In control of biology: of mice, men and Foxes.
Forkhead proteins comprise a highly conserved family of transcription factors, named after the original forkhead gene in Drosophila. To date, over 100 forkhead genes have been identified in a large variety of species, all sharing the evolutionary conserved 'forkhead' DNA-binding domain, and the cloning and characterization of forkhead genes have continued in recent years. Forkhead transcription factors regulate the expression of countless genes downstream of important signalling pathways in most, if not all, tissues and cell types. Recent work has provided novel insights into the mechanisms that contribute to their functional diversity, including functional protein domains and interactions of forkheads with other transcription factors. Studies using loss- and gain-of-function models have elucidated the role of forkhead factors in developmental biology and cellular functions such as metabolism, cell division and cell survival. The importance of forkhead transcription factors is underlined by the developmental defects observed in mutant model organisms, and multiple human disorders and cancers which can be attributed to mutations within members of the forkhead gene family. This review provides a comprehensive overview of current knowledge on forkhead transcription factors, from structural organization and regulatory mechanisms to cellular and developmental functions in mice and humans. Finally, we will discuss how novel insights gained from involvement of 'Foxes' in the mechanisms underlying human pathology may create new opportunities for treatment strategies.
Wijchers
Patrick J E C
PJ
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. patrick.wijchers@csc.mrc.ac.uk
Burbach
J Peter H
JP
Smidt
Marten P
MP
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry; D051858:Forkhead Transcription Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D051858:Forkhead Transcription Factors; D004247:DNA