Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagenase-1 (matrix metalloproteinase-1 (MMP-1)) degrades the extracellular matrix and enhances the invasive phenotype of tumor cells. v-src activated MMP-1 transcription through a series of elements in the proximal promoter, including the E2BP (nt -172), polyoma virus enhancer A3 (PEA3) (nt -94), activator protein-1 (AP-1) (nt -72), and signal transducer and activator of transcription (STAT) (nt -57) consensus sites. Of these sites, PEA3 and STAT contributed specifically to induction by v-src, whereas the remaining elements were also involved in induction by the phorbol ester phorbol myristate acetate (PMA). However, in contrast to MMP-1 induction by PMA, an AP-1 site located at nt -186 did not contribute to v-src induction. These results suggest divergence of the tyrosine kinase- and protein kinase C-dependent pathways with respect to MMP-1 transcription. v-src induced MMP-1 through mitogen-activated protein kinases, with extracellular signal-regulated kinases playing a larger role than c-jun N-terminal kinase. Retinoic acid, which inhibits the progression of certain cancers, repressed v-src-induced MMP-1 transcription. Constitutive expression of retinoic acid receptors (RARs) alpha or beta, but not gamma, or of retinoid X receptor alpha, repressed v-src-induced collagenase-1 transcription. We concluded that oncogenic induction of MMP-1 by v-src depends on signaling pathways and cis-acting sequences that are distinct from those involved in phorbol ester activation. Furthermore, v-src induction of MMP-1 may, by acting in concert with other genes, enhance matrix degradation and tumor progression, and retinoic acid and RARs may antagonize this induction in an RAR type-specific manner.
Mol Carcinog 1998 Mar
PMID:v-src activation of the collagenase-1 (matrix metalloproteinase-1) promoter through PEA3 and STAT: requirement of extracellular signal-regulated kinases and inhibition by retinoic acid receptors. 953 51

The expression of the fructose 1,6-bisphosphatase gene in HL-60 cells was induced by retinoic acid. The levels of mRNA, enzyme activity and enzyme protein in the cell line began to rapidly increase after culturing with retinoic acid for 72 h. Retinoic acid dose-dependently increased the enzyme activity with maximal stimulation at 1 microM. The responses of the fructose 1,6-bisphosphatase gene expression by retinoic acid were markedly slower than those of the enzyme expression by 1alpha,25-dihydroxyvitamin D3. When HL-60 cells were cultured in the presence of both retinoic acid and 1alpha,25-dihydroxyvitamin D3, the effects of the two agents on enzyme activity, protein and mRNA were additive.
Biochem Mol Biol Int 1998 Mar
PMID:Induction of fructose 1,6-bisphosphatase in HL-60 leukemia cells by retinoic acid. 955 8

Northern blot analysis of total RNA from a variety of rabbit tissues indicated that placenta is the primary site of expression of the protein hormone relaxin (previously called SQ10) in rabbits. Relaxin was not detected by this method in other rabbit tissues, including normal trachea and several squamous tissues. However, relaxin is highly induced during squamous cell differentiation in cultured rabbit tracheal epithelial (RbTE) cells. Retinoic acid and retinoids that selectively bind to the nuclear retinoid receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), and induce RARE- or RXRE-dependent transactivation as well as repression of AP-1-dependent transactivation, were all effective in suppressing relaxin expression. In addition, the retinoid SR11302, which exhibits only anti-AP-1 activity but does not induce RARE- or RXRE-dependent transactivation, was also able to inhibit relaxin expression. These results suggest that the suppression of relaxin expression is related to the anti-AP-1 activity of retinoids. To determine whether the relaxin gene is regulated by retinoids at the level of transcription, a 4.3 kb fragment of the 5' flanking region of the rabbit relaxin gene was cloned and analyzed. This regulatory region included a classic TATA-box as well as consensus sequences for several transcription factors, including CREB, NF-kappaB and AP-1. The ability of the 4.3 kb regulatory region to control the transcription of a luciferase reporter gene was analyzed in transiently transfected, squamous-differentiated RbTE cells. The results demonstrated that this regulatory region caused strong transactivation of the reporter gene. This transactivation was inhibited by retinoic acid, suggesting retinoid control at the transcriptional level. Deletion analysis indicated that multiple regulatory elements are involved in the regulation of relaxin gene expression during squamous differentiation as well as in the suppression by retinoids.
Mol Cell Endocrinol 1998 Mar 16
PMID:Suppression of relaxin gene expression by retinoids in squamous differentiated rabbit tracheal epithelial cells. 968 20

The APP gene promoter has multiple regulatory sequences, some of which may contribute to the neuropathology of Alzheimer's disease (AD). In this study, we investigated the effects of phorbol ester (PMA), IL-1, retinoic acid and reactive oxygen species on APP promoter activity in primary hippocampal neurons. We transfected neurons with either of two APP promoter constructs, a -2.8 kb and a shorter -488 bp upstream fragment fused to the chloramphenicol transferase (CAT) reporter gene. We demonstrated that phorbol 12-myristate-13 acetate (PMA), retinoic acid and IL-1 all stimulated both APP promoter constructs in hippocampal neurons after 24 h treatment. PMA and IL-1 treatments led to 2-fold increases of APP promoter activity. Retinoic acid induced a 3-fold increase. In addition, the magnitude of APP promoter responses to PMA and IL-1 treatment was similar between APP -2.8 kb and -488 bp plasmid transfected neurons. This suggests that the AP-1 sequence at -350 to -344 in the APP promoter may mediate the stimulatory effects of PMA and IL-1, as previously observed in endothelial and HeLa cells. In contrast, hydrogen peroxide, which was shown to activate NF-kappaB in primary neurons, failed to stimulate APP promoter activity, suggesting that the regulatory elements in the APP promoter may not respond to reactive oxygen species. Overall, these data indicate that APP expression in primary neurons can be modulated by PMA, IL-1 and retinoic acid. However, the contribution of reactive oxygen to Alzheimer's disease may not be directly related to the activation of the APP gene promoter but instead to neuronal damage associated with oxidative stress. Since elevated levels of IL-1 have been observed in AD brain, IL-1 could contribute to development of Alzheimer's disease by stimulating APP synthesis in primary neurons.
Brain Res Mol Brain Res 1998 Sep 18
PMID:Upregulation of amyloid precursor protein gene promoter in rat primary hippocampal neurons by phorbol ester, IL-1 and retinoic acid, but not by reactive oxygen species. 974 93

Retinoic acid (RA) is a high affinity ligand for a nuclear receptor which regulates transcription in target cells. Specific effects of RA on cardiac development and myocardial cell hypertrophy have been demonstrated; however, little information exists concerning RA-mediated regulation of cardiac genes. This study was initiated to investigate whether RA regulates Na,K-ATPase subunit gene expression in primary cultures of neonatal rat cardiac myocytes. Northern blot analyses demonstrated that NA, K-ATPase alpha3 subunit mRNA content was stimulated three-fold by RA. The effect of RA on alpha3 subunit gene expression was selective as RA treatment had no effect on either Na,K-ATPase alpha1, alpha2 or beta1 subunit mRNAs. A stimulatory effect of RA on Na,K-ATPase alpha3 gene transcription was not evident in either transient transfection or nuclear run-on studies, suggesting that augmentation of alpha3 mRNA content by RA was due to a post-transcriptional mechanism. Finally, RA diminished the magnitude of the thyroid hormone (T3)-mediated increase in Na,K-ATPase beta1 subunit mRNA, while RA had no effect on the stimulation of alpha3 mRNA content by T3.
J Mol Cell Cardiol 1998 Nov
PMID:Selective induction of Na,K-ATPase alpha3 subunit mRNA abundance in cardiac myocytes by retinoic acid. 992 75

The normal growth and differentiation of the epidermis require an adequate supply of vitamin A. The active form of vitamin A for normal epidermal homeostasis is retinoic acid (RA). Retinoic acid controls the expression of retinoid-responsive genes via interactions of the retinoic acid/nuclear receptor complexes at specific DNA sequences in their control regions. The message conveyed by RA is likely modulated by the concentration of the ligand available for binding to the receptors. Following the uptake of plasma retinol, epidermal keratinocytes synthesize retinoic acid via two sequential reactions with retinaldehyde as an intermediate. Several retinol dehydrogenase (RDH) enzymes, members of the short-chain dehydrogenase/reductase (SDR) gene superfamily, catalyze the first and rate-limiting step that generates retinaldehyde from retinol bound to cellular retinol-binding protein (holo-CRBP). However, little is known about these enzymes and their genes in the epidermal cells. Our work describes the first member of the RDH family found in epidermis. We show that this gene is expressed predominantly in the differentiating spinous layers and that it is under positive, feed-forward regulation by retinoic acid. It encodes a protein that, using NAD+ as a preferred cofactor, utilizes free and CRBP-bound all-trans-retinol and steroids as substrates.
Mol Genet Metab 1999 May
PMID:Cloning and characterization of retinol dehydrogenase transcripts expressed in human epidermal keratinocytes. 1032 26

Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR alpha mRNA was elevated whereas the levels of RAR gamma and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR alpha and gamma mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 microM RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines.
Mol Cell Endocrinol 1999 Jul 20
PMID:Retinoid and androgen regulation of cell growth, epidermal growth factor and retinoic acid receptors in normal and carcinoma rat prostate cells. 1045 51

Retinoic acid (RA) plays a pivotal role during vertebrate development, both as morphogen and as potent teratogen. While RA function in axial development has been extensively studied, little is known about the genetic control of RA teratogenicity. The knockout of the homeobox gene goosecoid in the mouse revealed similarities to RA induced embryopathy. We show that RA treatment of mouse gastrula embryos in vitro and of E10.5 embryos in utero led to a rapid but transient down-regulation of goosecoid expression. Repression was dependent on retinoid X receptors (RXR). BMP-4 was repressed by RA-treatment as well, both in embryos and in F9 teratocarcinoma cells. Our data suggest that both goosecoid and BMP-4 function as mediators of RA teratogenicity in mouse embryos.
Cell Mol Biol (Noisy-le-grand) 1999 Jul
PMID:Retinoic acid teratogenicity: the role of goosecoid and BMP-4. 1051 93

The Oct-4 gene encodes a transcription factor that is essential for maintaining the mouse germline. It is expressed during the earliest stages of embryogenesis, is downregulated during gastrulation, and is thereafter constrained to the germ cell lineage. Retinoic acid induced differentiation of embryonal carcinoma cells is also accompanied by a decrease in Oct-4 expression. We have previously shown that downregulation of Oct-4 expression is mediated by a hormone regulatory element (HRE). This element is located within the basal promoter and overlaps with a GC box that is crucial for Oct-4 promoter activity. The HRE is composed of three direct repeats with 1 and 0 spacing. In this study, we demonstrate that the doublet of direct repeats with 0 spacing (DR0) is bound by two novel factors. The initial repression of Oct-4 by retinoic acid coincides with the disappearance of the first factor (named UCF for undifferentiated cellular factor) and the appearance of a transiently induced factor (TRIF) which forms a larger complex with DR0 in electrophoretic mobility shift assays. These observations support the hypothesis that downregulation of the Oct-4 gene during early mouse embryogenesis involves the repression of its promoter by TRIF.
Cell Mol Biol (Noisy-le-grand) 1999 Jul
PMID:Repression of Oct-4 during embryonic cell differentiation correlates with the appearance of TRIF, a transiently induced DNA-binding factor. 1051 1

Phylogenetic relationships of 70 taxa representing 68 species of the Neotropical killifish family Rivulidae were derived from analysis of 1516 nucleotides sampled from four different segments of the mitochondrial genome: 12S rRNA, 16S rRNA, cytochrome oxidase I, and cytochrome b. The basal bifurcation of Cynolebiatinae and Rivulinae (Costa, 1990a,b) is supported; however, Terranatos, Maratecoara, and Plesiolebias are rivulins, not cynolebiatins. These three genera, along with the other recognized annual rivulin genera, form a monophyletic clade. Austrofundulus, Rachovia, Renova, Terranatos, and 3 species of the genus Pterolebias, all from northeastern South America, form a monophyletic clade excluding other species of Pterolebias. Pterolebias as presently understood is clearly polyphyletic. Trigonectes and Moema are supported as sister groups but do not form a monophyletic group with the genera Neofundulus and Renova as previously proposed. The suite of adaptations necessary for an annual life history has clearly been lost several times in the course of rivulid evolution. Also revealed is a considerable increase in substitution rate in most annual lineages relative to the nonannual Rivulus species. The widespread and speciose genus Rivulus is paraphyletic, representing both basal and terminal clades within the Rivulidae. Previous hypotheses regarding the vicariant origin of Greater Antillean Rivulus species are supported. Most rivulid clades show considerable endemism; thus, detailed analysis of rivulid phylogeny and distribution will contribute robust hypotheses to the clarification of Neotropical biogeography.
Mol Phylogenet Evol 1999 Nov
PMID:Phylogeny of the Neotropical killifish family Rivulidae (Cyprinodontiformes, Aplocheiloidei) inferred from mitochondrial DNA sequences. 1060 57


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