Isolation, regulation, and DNA-binding properties of three Drosophila nuclear hormone receptor superfamily members.

Fisk, Gregory J.; Thummel, Carl S.

doi:10.1073/pnas.92.23.10604

Cited by 99 publications

(82 citation statements)

References 39 publications

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“…NR4As bind to the NBRE (NGFI-B response element), through which NR4A2 regulates the mammalian TH promoter (Maxwell and Muscat, 2006). HR38 is the single Drosophila ortholog of the mammalian NR4A family and has been shown to bind to the NBRE (Baker et al, 2003;Fisk and Thummel, 1995). Consistent with this, it has recently been reported that HR38 binds to the NBRE-like sequence upstream of the Ddc gene and that ectopic expression of HR38 influences expression of Ddc in a tissue-dependent manner (Davis et al, 2007b).…”

Section: Hr38 Is Required For P38-dependent Melanizationsupporting

confidence: 50%

p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors

Sekine

Takagahara

Hatanaka

et al. 2011

Journal of Cell Science

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SummaryIn Drosophila, the melanization reaction is an important defense mechanism against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the dopamine synthesis pathway, underlie the melanin synthesis by providing the melanin precursors dopa and dopamine, respectively. It has been shown that expression of Drosophila TH and Ddc is induced in various physiological and pathological conditions, including bacterial challenge; however, the mechanism involved has not been fully elucidated. Here, we show that ectopic activation of p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization in the Drosophila cuticle. This p38-dependent melanization was attenuated by knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate a promoter containing NR4A-binding elements, with this transactivation being, at least in part, dependent on the phosphorylation. This suggests an evolutionarily conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene induction through NR4As appears to function in the dopamine synthesis pathway and may be involved in immune and stress responses.

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Section: Hr38 Is Required For P38-dependent Melanizationsupporting

confidence: 50%

p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors

Sekine

Takagahara

Hatanaka

et al. 2011

Journal of Cell Science

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“…Hence, if regulatory factors other than the EcR/USP heterodimer are involved positively in the ecdysteroid response mediated by the DR3G element, they remain to be identified. On the other hand, it has been recently reported that the Drosophila nuclear receptor Svp (78) and the newly identified orphan receptor XR78E/F-DHR78 (18,79) may inhibit ecdysone signaling pathways. These receptors bind preferentially to a DR1 element but are also able to bind to a DR3 element.…”

Section: Discussionmentioning

confidence: 99%

Direct Repeats Bind the EcR/USP Receptor and Mediate Ecdysteroid Responses in Drosophila melanogaster

Antoniewski

Mugat

Delbac

et al. 1996

Molecular and Cellular Biology

102

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The steroid hormone 20-hydroxyecdysone plays a key role in the induction and modulation of morphogenetic events throughout Drosophila development. Previous studies have shown that a heterodimeric nuclear receptor composed of the EcR and USP proteins mediates the action of the hormone at the transcriptional level through binding to palindromic ecdysteroid response elements (EcREs) such as those present in the promoter of the hsp27 gene or the fat body-specific enhancer of the Fbp1 gene. We show that in addition to palindromic EcREs, the EcR/USP heterodimer can bind in vitro with various affinities to direct repetitions of the motif AGGTCA separated by 1 to 5 nucleotides (DR1 to DR5), which are known to be target sites for vertebrate nuclear receptors. At variance with these receptors, EcR/USP was also found to bind to a DR0 direct repeat with no intervening nucleotide. In cell transfection assays, direct repeats DR0 to DR5 alone can render the minimum viral tk or Drosophila Fbp1 promoter responsive to 20-hydroxyecdysone, as does the palindromic hsp27 EcRE. In a transgenic assay, however, neither the palindromic hsp27 element nor direct repeat DR3 alone can make the Fbp1 minimal promoter responsive to premetamorphic ecdysteroid peaks. In contrast, DR0 and DR3 elements, when substituted for the natural palindromic EcRE in the context of the Fbp1 enhancer, can drive a strong fat body-specific ecdysteroid response in transgenic animals. These results demonstrate that directly repeated EcR/USP binding sites are as effective as palindromic EcREs in vivo. They also provide evidence that additional flanking regulatory sequences are crucially required to potentiate the hormonal response mediated by both types of elements and specify its spatial and temporal pattern.

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“…Interestingly, their misexpression produces slight reductions in the sensilla counts, indicating that these genes may also regulate ORN differentiation. The functions of Ches-1-like, and Hnf4 are unknown (Fisk and Thummel, 1995;Mazet et al, 2003). Although Hnf4 expression leads to a reduction in the number of trichoid sensilla, the distinct enlargement of the glomeruli indicates that Hnf4 may also have a separate role in glomerular development.…”

Section: Genes Encoding Transcription Factors and Transcription Factomentioning

confidence: 98%

Misexpression screen for genes altering the olfactory map in Drosophila

Zhang

Zhou

Yin

et al. 2006

Genesis

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Despite the identification of a number of guidance molecules, a comprehensive picture has yet to emerge to explain the precise anatomy of the olfactory map. From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that, when forcibly expressed in the olfactory receptor neurons, disrupted the stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not been shown previously to control olfactory map development, encode novel proteins as well as proteins with known roles in axonal outgrowth and cytoskeletal remodeling. We analyzed Akap200, which encodes a Protein Kinase A-binding protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200 validates our screen as an effective approach for recovering genes controlling glomerular map patterning. Our finding of diverse classes of genes reveals the complexity of the mechanisms that underlie olfactory map development.

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Isolation, regulation, and DNA-binding properties of three Drosophila nuclear hormone receptor superfamily members.

Cited by 99 publications

References 39 publications

p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors

p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway through phosphorylation of NR4A nuclear receptors

Direct Repeats Bind the EcR/USP Receptor and Mediate Ecdysteroid Responses in Drosophila melanogaster

Misexpression screen for genes altering the olfactory map in Drosophila

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