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E S Ong

Publications and source records attributed to E S Ong.

17 recordsLinked to original sources
PubMed1995

LXR, a nuclear receptor that defines a distinct retinoid response pathway.

We have identified a new retinoid response pathway through which 9-cis retinoic acid (9cRA) activates transcription in the presence of LXR alpha, a member of the nuclear receptor superfamily. LXR alpha shows a specific pattern of expression in visceral organs, thereby restricting the response to certain tissues. Retinoid trans-activation occurs selectively on a distinct response element termed an LXRE. Significantly, neither RXR homodimers nor RXR/RAR heterodimers are able to substitute for LXR alpha in mediating this retinoid response. We provide evidence that the retinoid response on the LXRE is the result of a unique interaction between LXR alpha and endogenous RXR, which, unlike in the RXR/RAR heterodimer, makes RXR competent to respond to retinoids. Thus, the interaction with LXR alpha shifts RXR from its role described previously as a silent, DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXREs.

Amino Acid Sequence↗
PubMed1992

Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.

An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXR alpha, beta, and gamma). They are closely related to each other in their DNA- and ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXR alpha. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXR alpha, beta, and gamma. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.

Amino Acid Sequence↗
PubMed1992

The occurrence of periodontitis-related microorganisms in relation to titanium implants.

The peri-implant space was examined for the presence of periodontitis-related microorganisms in 19 patients. All patients had been fitted with osseointegrated titanium implants which were clinically sound at the time of examination and all had been prescribed daily 0.2% chlorhexidine mouthrinse. In 17 patients, two contralateral fixtures in patients were selected, the remaining 2 patients had only one fixture, and associated mucosal clinical variables assessed for plaque accumulation, gingival inflammation, bleeding tendency, and probing depth. The bacteriological composition of submucosal plaque samples was investigated using non-selective media and selective media for Actinobacillus actimomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Prevotella intermedia (Pi). The peri-implant tissues were healthy. Twenty-two of 37 sites had a greater proportion of anaerobes than aerobes. Aa was detected at one site. Pg was not cultivated, and Pi was present in 7 of 37 sites, comprising between 0.4% and 60.9% of the total anaerobic viable counts. Since the presence of any of these organisms may play a contributory role to the loss of the fixture, it is recommended that the submucosal plaque of implants be monitored regularly for the presence of these periodontitis-associated species.

Adult↗
PubMed1991

A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR.

The vitamin A derivative retinoic acid exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). We provide evidence that expression of the gene for cellular retinol-binding protein type II (CRBPII), a key protein in the intestinal absorption of vitamin A, is dramatically up-regulated by retinoic acid in the presence of RXR but not RAR. This regulation is conferred through a specific cis element in the CRBPII promoter that contains five nearly perfect tandem repeats of the sequence AGGTCA spaced by a single nucleotide. The discovery of this new RX response element provides a means for distinguishing between the two retinoid receptor systems and suggests that an RXR-mediated pathway exists for modulating vitamin A metabolism.

Animals↗
PubMed1990

Nuclear receptor that identifies a novel retinoic acid response pathway.

Molecular cloning and transcriptional activation studies have revealed a new protein similar to the steroid hormone receptors and which responds specifically to vitamin A metabolites. This protein is substantially different in primary structure and ligand specificity from the products of the previously described retinoic acid receptor gene family. By indicating the existence of an additional pathway through which retinoic acid may exert its effects, these data lead to a re-evaluation of retinoid physiology.

Adult↗
PubMed1989

Spatial and temporal expression of the retinoic acid receptor in the regenerating amphibian limb.

Retinoic acid is known to have dramatic effects on vertebrate limb pattern in development and regeneration, supporting a model in which a gradient of retinoic acid serves as a morphogen to differentially supply positional information to a developing limb. The discovery of a retinoic acid receptor (RAR) and its homology to the steroid and thyroid hormone receptors provided a potential molecular mechanism for limb morphogenesis. One prediction of this model is that the receptor must be expressed in the developing and regenerating limb anlage. We investigated the expression of the RAR in the adult newt, Notophthalmus viridescens, whose amputated limbs are capable of regenerating and upon which retinoic acid can act to alter pattern. We report the cloning of cDNAs encoding a functional newt RAR and the localization of high and uniform levels of RAR mRNA specifically in the regenerating cells that control limb pattern. These results indicate that the morphogenic field is established through differential activation of pre-existing retinoic acid receptors rather than differential expression of the RAR gene.

Amino Acid Sequence↗
PubMed1988

The Drosophila gene knirps-related is a member of the steroid-receptor gene superfamily.

Molecular cloning has demonstrated that the receptors for steroid, retinoid and thyroid hormones are part of a large superfamily of nuclear regulatory proteins. In vertebrates these molecules regulate diverse biological processes such as pattern formation, cellular differentiation and homeostasis. The universal necessity for embryonic and adult cells to respond to their external environment might mean that members of this family pre-date the divergence of vertebrates and invertebrates. We have screened a Drosophila genomic library for steroid receptor homologues using a human retinoic acid receptor complementary DNA as a hybridization probe. Several clones were recovered, one of which mapped to chromosomal position 77E1-2, the cytological location of the gap segmentation gene knirps. Sequence analysis of a cDNA clone representing the human retinoic acid receptor homologue showed similarity of the predicted protein to the vertebrate steroid receptors, as well as to the predicted knirps gene product. In situ hybridization of a cDNA probe to wild-type embryos revealed a uniform distribution of transcripts that were apparently maternally derived. Zygotic transcript accumulation begins in a broad anteroventral domain before the cellular blastoderm stage. At the cellular blastoderm stage two additional circumferential bands of transcript appear.

Amino Acid Sequence↗
PubMed1985

Primary structure and expression of a functional human glucocorticoid receptor cDNA.

Identification of complementary DNAs encoding the human glucocorticoid receptor predicts two protein forms, of 777 (alpha) and 742 (beta) amino acids, which differ at their carboxy termini. The proteins contain a cysteine/lysine/arginine-rich region which may define the DNA-binding domain. Pure radiolabelled glucocorticoid receptor, synthesized in vitro, is immunoreactive and possesses intrinsic steroid-binding activity characteristic of the native glucocorticoid receptor.

Amino Acid Sequence↗
PubMed1985

Identification of human glucocorticoid receptor complementary DNA clones by epitope selection.

Steroid hormones regulate cellular differentiation and physiologic functions predominantly through gene transcription. Regulation is achieved by the interaction of specific steroid receptor proteins and target genes. Expression cloning techniques were used to select human glucocorticoid receptor complementary DNA clones in order to define the mechanism by which the receptor exerts its transcriptional control. Immobilized fusion proteins from individual clones were used to select epitope-specific antibody which was subsequently eluted and identified by binding to protein blots of cellular extracts. Three cross-hybridizing clones containing inserts expressing antigenic determinants of the human glucocorticoid receptor were isolated.

Cloning, Molecular↗
PubMed1984

Infectious and selectable retrovirus containing an inducible rat growth hormone minigene.

A growth hormone minigene carrying its natural promoter (237 nucleotides of chromosomal DNA) was stably propagated in a murine retrovirus containing hypoxanthine-guanine phosphoribosyltransferase as a selectable marker. Glucocorticoid and thyroid hormone inducibility was transferred with the growth hormone gene. Recombinant virus with titers of 10(6) per milliliter was recovered. This demonstration that retroviruses can be used to transfer a nonselectable gene under its own regulatory control enlarges the scope of retroviral vectors as potent tools for gene transfer.

Animals↗
PubMed1982

Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.

Alternative processing of RNA transcripts from the calcitonin gene results in the production of distinct mRNAs encoding the hormone calcitonin or a predicted product referred to as calcitonin gene-related peptide (CGRP). The calcitonin mRNA predominates in the thyroid while the CGRP-specific mRNA appears to predominate in the hypothalamus. These observations lead us to propose a model in which developmental regulation of RNA processing is used to increase the diversity of neuroendocrine gene expression.

Animals↗
PubMed1982

Calcitonin mRNA polymorphism: peptide switching associated with alternative RNA splicing events.

Evidence is presented which supports a model proposing that differential RNA splicing events may be used in expression of genes of the endocrine system to generate alternative polypeptide hormones. We previously reported that variation in the expression of the gene encoding the small polypeptide hormone calcitonin is associated with the production of a new calcitonin-like or pseudo-calcitonin (psi Cal) mRNA. A plasmid containing psi Cal cDNA sequences has been constructed, and calcitonin genomic clones have been isolated. Hybridization analysis reveals that calcitonin and psi Cal sequences are chromosomally linked and are present in the same nuclear RNA transcripts. Both calcitonin and psi Cal mRNAs are functional and encode different polypeptide products. These data are compatible with the proposed model that alternative RNA splicing of the transcript(s) of the calcitonin gene ultimately results in the production of different polypeptide products.

Amino Acid Sequence↗
PubMed1981

Altered expression of the calcitonin gene associated with RNA polymorphism.

The selective control of gene expression results in diversified morphology and physiological function. Understanding the expression of differentiated function in molecular terms requires detailed characterization of the regulation of mRNA synthesis and catabolism. Although considerable emphasis has been placed on transcriptional control, the discovery of HnRNA and 'split genes' gives rise to the possibility of post-transcriptional regulation at the level of processing of nuclear precursors. A rat calcitonin-producing medullary thyroid carcinoma (MTC) line was used as a model for definition of certain aspects in regulation of gene expression. Serial transplantation of several rat MTC lines containing and secreting large amounts of calcitonin generated tumours in which calcitonin biosynthesis was decreased more than 10-fold. We report here that the conversion from a 'high' to a 'low' calcitonin producing state is associated with specific modifications of the calcitonin mRNA synthetic pathway and a consequence of these changes seems to be the production of a new cytoplasmic mRNA.

Animals↗
PubMed1981

Thyrotropin-releasing hormone exerts rapid nuclear effects to increase production of the primary prolactin mRNA transcript.

This report directly documents that a polypeptide hormone can regulate specific gene expression as a consequence of increasing the levels of a primary genomic transcript. The regulation and expression of the prolactin gene was studied in a cell line (GH4) derived from a rat pituitary tumor. These cells respond to addition of the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH; thyroliberin), by elevation of the levels of mature prolactin mRNA and increase in prolactin biosynthesis. The message induction is preceded by, and apparently consequential to, a comparable rapid increase in the nuclear prolactin RNA precursors, including the putative primary transcript.

Animals↗
PubMedDate not supplied

The c-erb-A gene encodes a thyroid hormone receptor.

The cDNA sequence of human c-erb-A, the cellular counterpart of the viral oncogene v-erb-A, indicates that the protein encoded by the gene is related to the steroid hormone receptors. Binding studies with the protein show it to be a receptor for thyroid hormones.

Amino Acid Sequence↗
PubMedDate not supplied

Identification of a receptor for the morphogen retinoic acid.

Analysis of complementary DNA encoding a novel gene product reveals striking similarity to the steroid and thyroid hormone receptors. Binding and transcription activational studies show it to be a receptor for the vitamin A-related morphogen retinoic acid.

Amino Acid Sequence↗