Disease relevance of fkh

• The transcription factor Foxo1 protects beta-cells against oxidative stress induced by hyperglycemia and prevents beta-cell replication in insulin-resistant states [1].

High impact information on fkh

• Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO, prevents the decline in cardiac performance with age [2].
• The region-specific homeotic gene fork head (fkh) promotes terminal as opposed to segmental development in the Drosophila embryo [3].
• The fkh gene product, however, does not contain a known protein motif, such as the homeodomain or the zinc fingers, nor is it similar in sequence to any other known protein [3].
• P element-mediated germ-line transformation and sequence comparison of wild-type and mutant alleles identify the fkh gene within the cloned region. fkh is expressed in the early embryo in the two terminal domains that are homeotically transformed in fkh mutant embryos [3].
• The Drosophila forkhead transcription factor (dFOXO) activates d4E-BP transcription [4].

Biological context of fkh

• Aside from being involved in the control of decisions during embryonic development, fkh thus participates directly in the control of specialized functions of differentiated cells at later stages of development [5].
• We demonstrate that these binding sites are relevant to the transcriptional activation of Sgs-4 and show that Fork head also binds to the Sgs-4 ecdysone response unit in vivo [5].
• We rescue the secretory cell death in the fkh mutants and show that the rescued cells still do not invaginate [6].
• A placode-specific fkh enhancer was identified 10 kb from the coding sequence [7].
• In addition, we identified a binding site for FKH protein that appears to act in fkh autoregulation, keeping the gene active after SCR has disappeared from the placode [7].

Anatomical context of fkh

• Our findings suggest at least two roles for fkh in formation of the embryonic salivary glands: an early role in promoting survival of the secretory cells, and a later role in secretory cell invagination, specifically in the constriction of the apical surface membrane [6].
• In embryos mutant for fork head (fkh), which encodes a transcription factor homologous to mammalian hepatocyte nuclear factor 3beta (HNF-3beta), the secretory primordia are not internalized and secretory tubes do not form [6].
• The rescued fkh secretory cells undergo basal nuclear migration in the same spatial and temporal pattern as in wild-type secretory cells, but do not constrict their apical surface membranes [6].
• Metabolic Diapause in Pancreatic beta-Cells Expressing a Gain-of-function Mutant of the Forkhead Protein Foxo1 [1].
• Our knowledge of endoderm development is limited; however, recent studies suggest that cooperation between the HNF3/Fork head and GATA transcription factors is crucial for endoderm specification [8].

Associations of fkh with chemical compounds

• Two of the Fork head/SEBP2 binding sites are located within an ecdysone response unit which controls the tissue- and stage-specific responses of Sgs-4 to the steroid hormone 20-hydroxyecdysone [5].
• Functional analyses show decreased glucose utilization and insulin secretion in beta-cells overexpressing Foxo1 [1].
• By applying this method to many motifs and to a cluster set of yeast genes, we detected a similarity between Swi Five Factor and forkhead proteins and suggest that the currently unidentified Swi Five Factor is one of the yeast forkhead proteins [9].

Physical interactions of fkh

• Mobility shift assay in the presence of an anti-Fork head antibody demonstrated that the Fork head factor interacts with the TGTTTGC box shown to be involved in tissue-specific Sgs3 expression [10].

Regulatory relationships of fkh

• Our results allow efficient recognition of insect Fork head binding sites and we show that the putative Fork head cognate elements preferentially accumulate in the near upstream region of genes abundantly expressed in the labial gland [11].

Other interactions of fkh

• We propose that trh, hkb, and fkh may serve as "morphogenetic cassettes" responsible for forming tubular structures in a variety of tissues [12].
• We present a model proposing that trachealess is the crucial duct-specific gene that Fork head represses to distinguish pregland from preduct cells [13].
• We characterize a 37-bp element (fkh[250]) derived from the fork head (fkh) gene, a natural target of the Hox gene Sex combs reduced (Scr) [14].
• We have shown that sens expression is initiated in the salivary placodes by fork head (fkh), a winged helix transcription factor [15].
• Downregulation of the tissue-specific transcription factor Fork head by Broad-Complex mediates a stage-specific hormone response [16].

Analytical, diagnostic and therapeutic context of fkh

• 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 [17].

References