Dataset Information

The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator.

ABSTRACT: Hormones provide generalized signals that are interpreted in a specific spatial and temporal manner by a developing or reproducing multicellular organism. The ability to respond to hormones is determined by the competence of a cell or a tissue. The betaFtz-F1 orphan nuclear receptor acts as a competence factor for the steroid hormone 20-hydroxyecdysone (20E) in Drosophila melanogaster metamorphosis and mosquito reproduction. The molecular nature of the betaFtz-F1 action remains unclear. We report that the protein-protein interaction between betaFtz-F1 and a p160/SRC coactivator of the ecdysone receptor, FISC, is crucial for the stage-specific expression of the 20E effector genes during mosquito reproduction. This interaction dramatically increases recruitment of FISC to the functional ecdysone receptor in a 20E-dependent manner. The presence of betaFtz-F1 facilitates loading of FISC and the ecdysone receptor on the target promoters, leading to enhanced local histone H4 acetylation and robust activation of the target genes. Thus, our results reveal the molecular basis of competence for the stage-specific 20E response.

SUBMITTER: Zhu J

PROVIDER: S-EPMC1698532 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator.

Zhu Jinsong J Chen Li L Sun Guoqiang G Raikhel Alexander S AS

Molecular and cellular biology 20061002 24

Hormones provide generalized signals that are interpreted in a specific spatial and temporal manner by a developing or reproducing multicellular organism. The ability to respond to hormones is determined by the competence of a cell or a tissue. The betaFtz-F1 orphan nuclear receptor acts as a competence factor for the steroid hormone 20-hydroxyecdysone (20E) in Drosophila melanogaster metamorphosis and mosquito reproduction. The molecular nature of the betaFtz-F1 action remains unclear. We repor ...[more]

PMID: 17015464

Similar Datasets

Project description:Cancer initiation and maintenance of the transformed cell state depend on altered cellular signaling and aberrant activities of transcription factors (TFs) that drive pathological gene expression in response to cooperating genetic lesions. Deciphering the roles of interacting TFs is therefore central to understanding carcinogenesis and for designing cancer therapies. Here, we use an unbiased genomic approach to define a TF network that triggers an abnormal gene expression program promoting malignancy of clonal tumors, generated in Drosophila imaginal disc epithelium by gain of oncogenic Ras (Ras(V12)) and loss of the tumor suppressor Scribble (scrib(1)). We show that malignant transformation of the ras(V12)scrib(1) tumors requires TFs of distinct families, namely the bZIP protein Fos, the ETS-domain factor Ets21c and the nuclear receptor Ftz-F1, all acting downstream of Jun-N-terminal kinase (JNK). Depleting any of the three TFs improves viability of tumor-bearing larvae, and this positive effect can be enhanced further by their combined removal. Although both Fos and Ftz-F1 synergistically contribute to ras(V12)scrib(1) tumor invasiveness, only Fos is required for JNK-induced differentiation defects and Matrix metalloprotease (MMP1) upregulation. In contrast, the Fos-dimerizing partner Jun is dispensable for JNK to exert its effects in ras(V12)scrib(1) tumors. Interestingly, Ets21c and Ftz-F1 are transcriptionally induced in these tumors in a JNK- and Fos-dependent manner, thereby demonstrating a hierarchy within the tripartite TF network, with Fos acting as the most upstream JNK effector. Of the three TFs, only Ets21c can efficiently substitute for loss of polarity and cooperate with Ras(V12) in inducing malignant clones that, like ras(V12)scrib(1) tumors, invade other tissues and overexpress MMP1 and the Drosophila insulin-like peptide 8 (Dilp8). While ras(V12)ets21c tumors require JNK for invasiveness, the JNK activity is dispensable for their growth. In conclusion, our study delineates both unique and overlapping functions of distinct TFs that cooperatively promote aberrant expression of target genes, leading to malignant tumor phenotypes.

Dataset Information

The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator.

Publications

The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets