Disease relevance of kay

• Furthermore, overexpression of c-Jun and c-Fos results in fourfold activation of the promoter in PCC-4 embryonal carcinoma cells [1].

High impact information on kay

• Common and distinct roles of DFos and DJun during Drosophila development [2].
• This study establishes a direct link among JNK signaling, DFos phosphorylation, chromatin modification, and AP-1-dependent transcription and its importance in a developing organism [3].
• Drosophila Fos mediates ERK and JNK signals via distinct phosphorylation sites [4].
• Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation [5].
• This effect requires Fos-dependent transcriptional activation of a matrix metalloprotease gene mmp1 downstream of JNK [6].

Biological context of kay

• Drosophila kayak mutant embryos exhibit defects in dorsal closure, a morphogenetic cell sheet movement during embryogenesis [7].
• Here we show that kayak encodes D-Fos, the Drosophila homologue of the mammalian proto-oncogene product, c-Fos [7].
• Defects observed in mutant embryos, and adults with reduced Fos expression, are reminiscent of phenotypes caused by 'loss of function' mutations in the Drosophila JNKK homologue, hemipterous [7].
• Drosophila puckered regulates Fos/Jun levels during follicle cell morphogenesis [8].
• The mammalian proto-oncogenes c-jun and c-fos are situated at the end of multiple signal transduction pathways and activation of their products Jun and Fos, components of the transcription factor AP-1, are able to regulate gene transcription in response to extracellular stimuli [9].

Anatomical context of kay

• Response of Djun and Dfos mRNA abundance to signal transduction pathways in cultured cells of Drosophila melanogaster [9].
• Finally, we show that Dfos is required in follicle cells for the dumping of the nurse cell cytoplasm into the oocyte and the subsequent apoptosis of nurse cells [10].
• Top-DER- and Dpp-dependent requirements for the Drosophila fos/kayak gene in follicular epithelium morphogenesis [10].
• In contrast, Dfos is required for the proper timing of larval salivary gland cell death as well as the proper induction of key death genes [11].
• Thorax closure in Drosophila: involvement of Fos and the JNK pathway [12].

Associations of kay with chemical compounds

• AP-1 activity is controlled, in part, by the redox state of critical cysteine residues within the basic regions of Jun and Fos [13].
• Basic leucine zipper proteins Jun and Fos form the dimeric transcription factor AP-1, essential for cell differentiation and immune and antioxidant defenses [13].
• Proinflammatory cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by activating transcription factors such as NF-kappaB and AP-1 [14].

Physical interactions of kay

• An AP-1 binding site in the upstream region of Deb-A is part of a developmentally regulated negative element [15].

Enzymatic interactions of kay

• Drosophila JNK and ERK phosphorylate D-Fos with overlapping, but distinct, patterns [4].

Regulatory relationships of kay

• The cAMP-mediated pathway positively regulates Dfos but negatively regulates Djun [9].
• The receptor tyrosine kinase pathways positively regulate Dfos and Djun [9].
• We show that Dfos expression is stimulated by Egfr signalling [16].
• Transcription of Dfos is stimulated by brain tumours of l(2)gl-deficient larvae of Drosophila melanogaster [17].

Other interactions of kay

• Strikingly, decreased or increased puc function leads to a corresponding increase or decrease, respectively, of Fos and Jun protein levels [8].
• Consistent with this, overexpression of a dominant negative DRac1 resulted in lower levels of Fos/Jun [8].
• This suggests that Puc acts downstream of the JNK pathway and D-Fos to mediate a negative feed-back loop [12].
• D-Fos, a target gene of Decapentaplegic signalling with a critical role during Drosophila endoderm induction [18].
• In overexpression assays, Pk1 is able to activate AP-1-mediated transcription and inhibit activation of Wnt/beta-catenin signaling [19].

Analytical, diagnostic and therapeutic context of kay

• High molecular weight DNA-protein complexes on an oligonucleotide probe spanning the AP-1 binding site were identified in gel retardation assays using partially purified bacterially expressed Djun protein or nuclear extracts from Drosophila embryos [15].
• To gain further insight into the function and the regulation of this gene, we have investigated the expression pattern of the two kay mRNA isoforms, kay-RA and kay-RB, during oogenesis and embryogenesis by whole-mount in situ hybridization [20].
• The RNA interference-mediated inhibition of Fos in proliferating cells of the wing and eye discs resulted in a specific defect in the G(2)-to-M-phase transition, while cell growth remained unimpaired, resulting in a marked reduction in organ size [21].

References