0000000000041339
AUTHOR
Christina Zechel
showing 6 related works from this author
The germ cell nuclear factor (GCNF)
2005
The germ cell nuclear factor (GCNF), which is also known as RTR (retinoid receptor-related testis-associated receptor) is a member of the nuclear receptor superfamily. As a natural ligand remains to be discovered, GCNF is referred to as an orphan receptor. Owing to GCNF's unique features and its distant relation to any other known nuclear receptor it has been classified as the only member of the subgroup six and designated NR6A1 by the Receptor Nomenclature Committee (Duarte et al., 2002: Nucleic Acids Res 30: 364-368). To date, GCNF has been cloned from distinct vertebrate species, including zebrafish, Xenopus laevis, mouse, rat, and human. Cloning and characterization of the gene, domain …
The expression level of the orphan nuclear receptor GCNF (germ cell nuclear factor) is critical for neuronal differentiation.
2004
The germ cell nuclear factor (GCNF) is essential for normal embryonic development and gametogenesis. To test the prediction that GCNF is additionally required for neuronal differentiation, we used the mouse embryonal carcinoma cell line PCC7-Mz1, which represents an advantageous model to study neuronal cells from the stage of fate choice until the acquirement of functional competence. We generated stable transfectants that express gcnf sense or antisense RNA under the control of a tetracycline-regulated promoter. After retinoic acid-induced withdrawal from the cell cycle, sense clones developed a neuron network with changed properties, and the time course of neuron maturation was shortened.…
The expression level of GCNF affects fate choice during neural differentiation of PCC7 cells
2005
The nuclear receptor GCNF (NR6A1) is required for embryonic survival and development, and regulation of fertility. We used a transgenic approach to investigate its role in neural differentiation. As model we chose the embryonal carcinoma cell line PCC7, which reproducibly differentiates into a tissue-like pattern of neuronal and non-neuronal cells after exposure to retinoic acid (RA). The differentiation pattern of gcnf sense and antisense clones consistently indicated that the expression level of GCNF positively correlated with the development of the neuronal fate. Moreover, antisense clones failed to down-regulate expression of the key regulator of differentiation Oct4 during the initial …
Co-regulator recruitment and the mechanism of retinoic acid receptor synergy.
2002
Crystal structure and co-regulator interaction studies have led to a general mechanistic view of the initial steps of nuclear receptor (NR) action. Agonist-induced transconformation of the ligand-binding domain (holo-LBD) leads to the formation of co-activator complexes, and destabilizes the co-repressor complexes bound to the ligand-free (apo) LBD. However, the molecular basis of retinoid-X receptor (RXR) 'subordination' in heterodimers, an essential mechanism to avoid signalling pathway promiscuity, has remained elusive. RXR, in contrast to its heterodimer partner, cannot autonomously induce transcription on binding of cognate agonists. Here we show that RXR can bind ligand and recruit co…
Requirement of Retinoic Acid Receptor Isotypes α, β, and γ during the Initial Steps of Neural Differentiation of PCC7 Cells
2005
Retinoic acid (RA) is indispensable for morphogenesis and differentiation of several tissues, including the nervous system. The requirement of the RA receptor (RAR) isotypes alpha, beta, and gamma and the putative role of retinoid X receptor-(RXR) signaling in RA-induced neural differentiation, was analyzed. For this compound-selective retinoids and the murine embryonal carcinoma cell line PCC7, a model system for RA-dependent neural differentiation was used. The present paper shows that proliferating PCC7 cells primarily express RXRalpha and RARalpha, lower levels of RXRbeta, and barely detectable amounts of RARbeta, RARgamma, and RXRgamma. At receptor-selective concentrations, only a RARa…
Synthetic retinoids dissociate coactivator binding from corepressor release.
2002
The ligand-activated retinoid receptors RXR and RAR control development, homeostasis and disease by regulating transcription of retinoic acid (RA) responsive target genes or crosstalk with other signalling pathways. According to the current model ligand-binding triggers an exchange between corepressor- and coactivator-complexes that inhibit or potentiate transcription by deacetylating and acetylating nucleosomal histones, respectively. Additional cofactors may modify the transcriptional regulatory process by linking liganded retinoid receptors to structural components of chromatin or protein degradation. The desire to specifically influence defined events in RA-signalling, while others are …