Five years on the wings of fork head

Kaufmann, Eckhard; Knöchel, Walter

doi:10.1016/0925-4773(96)00539-4

Cited by 610 publications

(443 citation statements)

References 118 publications

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“…This domain consists of three alpha-helices connected by two polypeptide loops, or 'wings,' which are related to the 'helix-turn-helix' domain found in homeobox-containing proteins. Forkhead box-containing proteins have been identified in eukaryotic organisms from yeast to humans, and have been shown to play important roles in various biological processes, including development, metabolism, immunoregulation, development of cancer, and aging (Carlsson & Mahlapuu, 2002;Coffer & Burgering, 2004;Jonsson & Peng, 2005;Kaufmann & Knochel, 1996;Lehmann et al, 2003). The nomenclature for the chordate forkhead transcription factors has been revised, and these genes, now termed 'Fox' (after 'Forkhead box'), are divided into seventeen subclasses, or clades, (A to Q), based on the amino acid (AA) sequence of their conserved forkhead domain (Kaestner et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Forkhead transcription factors regulate mosquito reproduction

Hansen

Sieglaff

Munro

et al. 2007

Insect Biochemistry and Molecular Biology

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Forkhead box (Fox) genes encode a family of transcription factors defined by a 'winged helix' DNAbinding domain. In this study we aimed to identify Fox factors that are expressed within the fat body of the yellow fever mosquito Aedes aegypti, and determine whether any of these are involved in the regulation of mosquito yolk protein gene expression. The Ae. aegypti genome contains eighteen loci that encode putative Fox factors. Our stringent cladistic analysis has profound implications for the use of Fox genes as phylogenetic markers. Twelve Ae. aegypti Fox genes are expressed within various tissues of adult females, six of which are expressed within the fat body. All six Fox genes expressed in the fat body displayed dynamic expression profiles following a blood meal. We knocked down the 'fat body Foxes' through RNAi to determine whether these "knockdowns" hindered amino acidinduced vitellogenin gene expression. We also determined the effect of these knockdowns on the number of eggs deposited following a blood meal. Knockdown of FoxN1, FoxN2, FoxL, and FoxO, had a negative effect on amino acid-induced vitellogenin gene expression and resulted in significantly fewer eggs laid. Our analysis stresses the importance of Fox transcription factors in regulating mosquito reproduction.

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Section: Introductionmentioning

confidence: 99%

Forkhead transcription factors regulate mosquito reproduction

Hansen

Sieglaff

Munro

et al. 2007

Insect Biochemistry and Molecular Biology

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“…Members of this family have been shown to play roles in cell proliferation, differentiation and metabolic homeostasis (Kaufmann and Knochel, 1996;Zaret, 1999;Kaestner et al, 2000;Costa et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27Kip1

et al. 2005

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We have previously shown that the breast cancer susceptibility gene, BRCA1, can transcriptionally activate the p27 Kip1 promoter. The BRCA1-responsive element was defined as a 35 bp region from position À545 to À511. We next determined that within this region is also a potential binding site for the transcription factor Forkhead box (FOX)A1. RNA and protein analysis as well as immunohistochemistry showed that expression of FOXA1 correlated with the expression of the estrogen receptor in a panel of breast cancer cell lines and tissues. In transient transfection reporter assays, FOXA1 could activate the p27 Kip1 promoter. Cotransfection of BRCA1 and FOXA1 resulted in a synergistic activation of the p27 Kip1 promoter. Mutation of the FOXA1 DNA-binding site in the p27 Kip1 promoter-luciferase construct significantly diminished the activity of FOXA1 alone or in combination with BRCA1. Cotransfection of FOXA1 and BRCA1 resulted in a greater amount of each protein compared to transfection of each expression vector alone. The half-life of FOXA1 was increased when coexpressed with BRCA1. Electrophoretic mobility shift assay analysis demonstrated that FOXA1 could bind to a wild-type oligonucleotide containing the FOXA1 binding site in the p27 Kip1 promoter, but this binding was lost upon mutation of this FOXA1 binding site. The protein-DNA binding complex could be supershifted with an antibody directed against FOXA1. The activity of the p27 Kip1 promoter as well as FOXA1 expression was reduced in cells treated with BRCA1 siRNA, thus silencing the expression of BRCA1 protein. In summary, we identified a FOXA1 binding site within the BRCA1-responsive element of the p27 Kip1 promoter and showed that FOXA1 activated the promoter alone and in conjunction with BRCA1. Furthermore, we identified high expression of FOXA1 in breast cancer cell lines and tissues, discovered a role for BRCA1 in the regulation of p27 Kip1 transcription and a possible interaction with BRCA1.

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“…All of these genes appear to encode transcription factors, which share a ϳ110 amino acid domain with high sequence similarity that serves as a DNA-binding domain (reviewed in Kaufmann and Knö chel, 1996). This domain has been termed forkhead domain after the founding member of this protein family, and based upon its structural features, it is also called winged helix domain.…”

Section: Introductionmentioning

confidence: 99%

Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns

Lee

Frasch

2004

Developmental Dynamics

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Genetic approaches in Drosophila led to the identification of Forkhead, the prototype of forkhead domain transcription factors that are now known to comprise an evolutionarily conserved family of proteins with essential roles in development and differentiation. Sequence analysis of the recently published genomic scaffold sequence from Drosophila melanogaster has allowed us to determine the presumably full complement of forkhead domain encoding genes in this species. We show herein that the Drosophila genome contains 17 forkhead domain encoding genes; 13 of these genes have orthologs in chordate species, and their products can be assigned to 10 of the 17 forkhead domain subclasses known from chordates. One Drosophila forkhead domain gene only has a Caenorhabditis elegans ortholog and may represent a subclass that is absent in chordates, while the remaining three cannot be classified. We present the mRNA expression patterns of seven previously uncharacterized members of this gene family and show that they are expressed in tissues from all three germ layers, including central and peripheral nervous system, epidermis, salivary gland primordia, endoderm, somatic mesoderm, and hemocyte progenitors. Furthermore, the expression patterns of two of these genes, fd19B and fd102C, suggest a role for them as gap genes during early embryonic head segmentation.

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Five years on the wings of fork head

Cited by 610 publications

References 118 publications

Forkhead transcription factors regulate mosquito reproduction

Forkhead transcription factors regulate mosquito reproduction

BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27Kip1

Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns

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