Fox's in development and disease

Lehmann, Ordan J.; Sowden, Jane C.; Carlsson, Peter; Jordan, Tim; Bhattacharya, Siladitya

doi:10.1016/s0168-9525(03)00111-2

Cited by 315 publications

(255 citation statements)

References 61 publications

Supporting

Mentioning

250

Contrasting

Unclassified

Order By: Relevance

“…FOXC1 is suggested to have a key role in cardiac, renal, ocular and cerebral morphogenesis. 19 During mouse embryogenesis, both Pitx2 and Foxc1 are expressed in the organs and tissues affected in ARS. In the developing mouse eye, Pitx2 and Foxc1 are co-localized in periocular mesenchyme and they interact physically through crucial functional domains.…”

Section: Pitx2 and Foxc1mentioning

confidence: 99%

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

2009

View full text Add to dashboard Cite

In association withAxenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations Axenfeld -Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations.

show abstract

Section: Pitx2 and Foxc1mentioning

confidence: 99%

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

2009

View full text Add to dashboard Cite

show abstract

“…We have now identified the cell-specific protein as the forkhead protein Foxa2 (formerly HNF-3␤). Foxa2 is a member of the forkhead family of winged helix DNA binding proteins that play roles in embryogenesis, tumorogenesis, and maintenance of cell differentiation (27,28). Foxa2 has been proposed to act by remodeling chromatin and to functionally interact with multiple factors (26, 29 -32).…”

Section: Foxa2 and Usf Activation Of Ct/cgrpmentioning

confidence: 99%

Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein

Viney

Schmidt

Gierasch

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

An 18-bp enhancer controls cell-specific expression of the calcitonin/calcitonin gene-related peptide gene. The enhancer is bound by a heterodimer of the bHLH-Zip protein USF-1 and -2 and a cell-specific factor from thyroid C cell lines. In this report we have identified the cell-specific factor as the forkhead protein Foxa2 (previously HNF-3␤). Binding of Foxa2 to the 18-bp enhancer was demonstrated using electrophoretic mobility shift assays. The cell-specific DNA-protein complex was selectively competed by a series of Foxa2 DNA binding sites, and the addition of Foxa2 antiserum supershifted the complex. Likewise, a complex similar to that seen with extracts from thyroid C cell lines was generated using an extract from heterologous cells expressing recombinant The calcitonin/calcitonin gene-related peptide (CT 1 /CGRP) gene expresses the hormone CT in thyroid C cells and the neuropeptide CGRP in neurons. CT is a therapeutically useful modulator of bone metabolism and calcium homeostasis (1), but it may also play additional roles based on the recent unexpected finding of increased bone mass in CT/CGRP and CT receptor knock-out mice (2-4). CGRP is an alternative splicing product from the CT/CGRP gene (5) that is now appreciated to be a member of a gene family of multifunctional neuropeptides that act on related receptors (6 -8). Most notably, CGRP is the most potent peptide dilator known (9, 10), and abnormal levels of CGRP have been implicated in neurovascular and cardiovascular disorders (7,(11)(12)(13). Importantly, CGRP antagonists have recently been reported to be an effective treatment for migraine (14).Regulation of CGRP expression in response to extracellular stimuli is controlled exclusively at the transcriptional level. Studies on both the human and rat CT/CGRP gene have identified a cell-specific enhancer containing helix-loop-helix (HLH) motifs ϳ1 kb upstream of the transcription start site (15-19). We have shown that an 18-bp element with a single HLH site and a flanking octamer-like motif is both sufficient and necessary for cell-specific enhancer activity (18, 19). Using nuclear extracts prepared from the neuronal-like CA77 thyroid C cell line, bHLH-Zip proteins USF-1 and -2 were shown to bind the enhancer in vitro (19). Although Oct1 can bind the A/T-rich half of the flanking site, Oct1 cannot transactivate the enhancer (18). Instead, a cell-specific protein referred to as OB2 was shown to bind an adjacent 8-bp site that partially overlaps the HLH site (19). OB2 was identified as an ϳ68-kDa protein by UV-cross-linking and is present in human and rat thyroid C cell lines but not in cell lines that do not express the CT/CGRP gene (19).In this study have shown that OB2 is the forkhead protein Foxa2, formerly called HNF-3␤. We demonstrate that Foxa2 is able to bind and activate the CT/CGRP enhancer in heterologous cells. Importantly, this transactivation requires the adjacent HLH site and is increased upon co-expression of USF. The combinatorial role of Foxa2 and USF was further demonstrated by short...

show abstract

“…The FOX proteins display large functional diversity and play a wide range of roles in development, proliferation, differentiation, stress resistance, apoptosis and control of metabolism (recently reviewed by Carlsson and Mahlapuu, 2002;Lehmann et al, 2003;Greer and Brunet, 2005;and van der Horst and Burgering, 2007). Their name is derived from the Drosophila melanogaster forkhead gene, the first identified FOX transcription factor, which is important for the correct formation of the anterior and posterior gut of the embryo (Weigel et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Structure/function relationships underlying regulation of FOXO transcription factors

2008

View full text Add to dashboard Cite

The FOXO subgroup of forkhead transcription factors plays a central role in cell-cycle control, differentiation, metabolism control, stress response and apoptosis. Therefore, the function of these important molecules is tightly controlled by a wide range of protein-protein interactions and posttranslational modifications including phosphorylation, acetylation and ubiquitination. The mechanisms by which these processes regulate FOXO activity are mostly elusive. This review focuses on recent advances in structural studies of forkhead transcription factors and the insights they provide into the mechanism of DNA recognition. On the basis of these data, we discuss structural aspects of protein-protein interactions and posttranslational modifications that target the forkhead domain and the nuclear localization signal of FOXO proteins.

show abstract

Fox's in development and disease

Cited by 315 publications

References 61 publications

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations

Regulation of the Cell-specific Calcitonin/Calcitonin Gene-related Peptide Enhancer by USF and the Foxa2 Forkhead Protein

Structure/function relationships underlying regulation of FOXO transcription factors

Contact Info

Product

Resources

About