Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between estrogen receptor(R) binding by uterine nuclei and uterotrophic responses was examined. Immature rats received a single injection of estradiol (E2) or estriol (E3) and the following parameters were measured: accumulation and retention of the estrogen receptor by the nuceus of uterine cells; incorporation of 14C-glucose into CO2 lipid, protein and RNA; RNA polymerase activity; water imbibition and increased dry weight. E2 and E3 were of equal potency with regard to the rapid accumulation of R by the nucleus but differed with respect to long term retention of R. The concentrations of nuclear RE2 and RE3 complexes were equivalent between 1 and 3 hr after estrogen injection; however, by 6 hr RE2 remained significantly elevated while RE3 levels had fallen to control values. E2 and E3 were also of equal potency with respect to the stimulation of enhanced glucose utilization, water imbibition, the incorporation of 14C-glucose into lipid, protein and RNA 3 hours following an injection of the hormone. Likewise the activity of RNA polymerase was equally stimulated by E2 and E3 3 hr after injection. Thus all early uterotropic responses (0-3 hrs) that were measured were equally stimulated by E2 and E3. However, E3 failed to stimulate true uterine growth (increase dry weight 24 hr after injection), whereas E2 produced a significant stimulation of true uterine growth. These data suggest that the RE complex is capable of stimulating early uterotrohic events regardless of which estrogen is present; however, in order to produce true uterine growth the RE complex must be retained in the nucleus for long periods of time. This proposal was tested by the administration of repetitive injections of E3. This treatment resulted in an increase in dry weight that was equivalent to the growth that was produced by repetitive injections of E2. These results demonstrate that E2 and E3 elicit early uterotrophic responses with equal facility following a single injection but that only E2 causes true uterine growth. The ability of E2 to stimulate true uterine growth appears to be related to the time of residence of the RE complex in the nucleus.
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PMID:Estrogen-induced uterine responses and growth: relationship to receptor estrogen binding by uterine nuclei. 16 76

Incubation of estradiol in vitro at 25 degrees C with homogenates of carcinogen-induced mammary tumors of ovariectomized rats stimulated the magnesium-dependent RNA polymerase activity of nuclei of the hormone-dependent (HD) (regressing) tumors, but had no effect on this activity in nuclei of hormone-independent (HI) (growing) tumors. Furthermore, recombination of the nuclei and cytosol fractions of HD and HI tumors indicated that the in vitro effect of estradiol on subsequent tumor nuclear RNA synthesis required the estrogen receptor-containing cytosol but was specific to nuclei of the HD tumor. This constituted the first direct in vitro effect of estrogen on a specific biochemical process in an HD mammary tumor.
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PMID:Estrogen-dependent in vitro stimulation of RNA synthesis in hormone-dependent mammary tumors of the rat. 16 35

Estrogen (diethylstilbesterol) was administered in vivo to chicks for various time periods. Chromatin was then prepared from oviduct nuclei and assayed for its capacity to support initiation of RNA chain synthesis in vitro in the presence of saturating levels of Escherichia coli RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase; EC 2.7.7.6). These same nuclei were also assayed by a [3H]estradiol exchange assay for their endogenous receptor content. The number of available initiation sites for RNA synthesis on chromatin was shown to correlate with the endogenous levels of nuclear estrogen receptor. A decrease in the nuclear concentration of estrogen receptor molecules and the concentration of initiation sites for RNA synthesis occurred during withdrawal of estrogen from previously stimulated chicks. Both parameters declined with a similar half-life. When estrogen was readministered to withdrawn chicks, the number of initiation sites increased 2-fold as early as 30 min and approached a maximal level (3-fold) by 1 hr. During the same period of restimulation with estrogen, the number of estrogen receptor molecules bound to nuclei increased to a maximum at 20 min and then declined at 1 hr to a steady-state level 2-fold higher than the withdrawn chicks. Simultaneous measurements of RNA chain length and RNA chain propagation rate demonstrated that parameters remained relatively constant throughout estrogen withdrawal as well as secondary stimulation. The temporal correlation between changes in the levels of nuclear-bound estrogen receptor and the number of RNA chain initiation sites on chromatin prepared from these same nuclei strongly suggested that the hormone receptor complexes act on chromatin to mediate these changes in genetic transcriptional activity.
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PMID:Effects of estrogen on gene expression in chick oviduct: nuclear receptor levels and initiation of transcription. 17 99

The [3H]estradiol exchange assay was used to characterize the nuclear estrogen receptor from the chick oviduct. After diethylstilibestrol (DES) treatment (14 days), the oviduct nuclei contained estrogen receptors that manifested high affinity (Kd = 2 X 10(-9)M) and low capacity binding (4000 to 5000 sites/cell) for estradiol. DES and estradiol competed significantly for [3H]estradiol binding, while testosterone and progesterone were ineffective. These binding sites were found in the oviduct and liver but not in the spleen, kidney, or muscle. Following salt extraction from nuclei, the receptor had a sedimentation coefficient of 4 S when analyzed by centrifugation in high and low salt sucrose density gradients. The [3H]estradiol exchange assay was used to examine the relationships between nuclear-bound receptor and RNA polymerase initiation sites on oviduct chromatin. Within 20 min after a single injection of 2.5 mg of DES to withdrawn chicks, a maximum number of estradiol receptor-binding sites was detected in oviduct nuclei. Within 30 min after DES injection, the total number of RNA initiation sites also increased, reaching 100% of control values. Daily injections of DES to unstimulated chicks resulted in a gradual increase in the nuclear content of estradiol receptor, which reached a maximum at 6 days and thereafter declined gradually up to 18 days of hormone treatment. A maximum number of initiation sites for RNA synthesis was also attained at 4 to 6 days of DES treatment and thereafter declined. When DES was withdrawn after 14 to 18 days of hormone stimulation, the numbers of nuclear estradiol receptor sites and initiation sites for RNA synthesis both declined gradually, reaching half-maximal values in 3 days and approached control values after 7 to 8 days of withdrawal. The increase in the concentration of nuclear estradiol receptor sites and the number of initiation sites for RNA synthesis also showed a close correlation with the dosage of DES administration. Both attained maximum levels at 1.25 mg of DES with a half-maximal value of 0.5 mg. The close correlation between the concentration of nuclear-bound estradiol receptors and the number of initiation sites for RNA synthesis in vivo is at present only a temporal correlation but does raise the possibility that gene transcription in chick oviduct may depend upon the amount of estradiol receptor bound to the target cell nuclei.
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PMID:Effect of estrogen on gene expression in the chick oviduct. Correlation between nuclear-bound estrogen receptor and chromatin initiation site for transcription. 17 20

The effects of estradiol and nafoxidine on nuclear estrogen receptor binding, RNA polymerase activities, and uterine ultrastructure were studied. Animals were either injected with estradiol, implanted with estradiol/paraffin pellets, or injected with nafoxidine. Animals treated with nafoxidine or estradiol implants showed sustained long-term nuclear retention of estrogen receptor and increased nuclear RNA polymerase activities for up to 72 hr. A single injection of estradiol caused initial increases in these variables which returned to control levels by 24 hr after hormone treatment. Uterine tissue was examined by light and electron microscopy 72 hr after hormone treatments. Uteri from eith estradiol-implanted or nafoxidine-treated animals showed markedly increased hypertrophy of the luminal epithelial cells. Nuclei in sections of the uteri of these hyperestrogenized animals displayed a large number and wide array of nuclear bodies composed of a filamentous capsule and granular cores. We conclude that hyperestrogenization, a condition that eventually results in abnormal cell growth, is correlated with increased and sustained nuclear binding of the estrogen receptor, increased and sustained RNA polymerase activity, and the appearance of nuclear bodies.
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PMID:Role of estrogen receptor binding and transcriptional activity in the stimulation of hyperestrogenism and nuclear bodies. 27 47

The antiestrogen tamoxifen has been used successfully in the treatment of breast cancer. In an attempt to elucidate its mode of action, its effects on steroid hormone receptor concentration and RNA polymerase activities in the uteri of ovariectomized rats have been compared with those of estradiol. A single dose of estradiol and tamoxifen, separately or in combination, produced slight increases in uterine wet weight 12 h after injection. Whereas both estradiol and tamoxifen could promote translocation of the estrogen receptor, only estradiol caused cytoplasmic replenishment of the receptor. Both compounds, separately and in combination, stimulated the production of cytoplasmic progesterone receptor 12 h after treatment. Estradiol produced and maintained significant elevations in RNA polymerase I activity, whereas the effects on this enzyme brought about by taxoxifen were less and transitory. However, estrogen and antiestrogen caused equal increases in RNA polymerase II activity, but, again, the effects of taxoxifen were shortlived when compared to those brought about by estradiol. Stimulation of RNA polymerase II activity was due to the availability of increased numbers of apparent initiation sites. These results point to a basic inefficacy in the antiestrogen-receptor complex; although it is able to promote early tissue responses characteristic of an estrogen, these cannot be sufficiently maintained.
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PMID:Effects of estradiol and the antiestrogen tamoxifen on steroid hormone receptor concentration and nuclear ribonucleic acid polymerase activities in rat uteri. 49 77

The in vitro transcription of chick liver chromatin before and after estrogen treatment was studied. Transcription was by endogenous as well as homologous exogenous RNA polymerase II and the products were analyzed for size and specific vitellogenin sequences. Quantitatively more RNA was synthesized from chromatin of 24 h estrogen-treated (E 24) chicks than from that of untreated chicks. In either case the size of transcribed RNA ranged from 5S to larger than 28S and most was between 5S and 18S. When a fraction enriched in estrogen receptor (E-Rec) complex was added to chromatin from untreated chicks, a dramatic shift of the RNA transcribed into heavier regions occurred. Analysis of RNA transcripts by hybridization to cDNAvit showed an equal number of sequences transcribed from E 24 chromatin and control; however, 13 times more specific sequences were transcribed in the presence of E-Rec complex. The results indicate the E-Rec complex exerts a regulatory function in the specific transcription of the vitellogenin gene.
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PMID:In vitro transcription of vitellogenin sequences on chick liver chromatin. 72 4

We have shown previously that estradiol, estriol, and Nafoxidine (Upjohn 11, 100A) have differential effects on uterine growth and that these effects are associated with the retention of the estrogen receptor by the nucleus. In order to examine these relationships further, we have studied the effect of these hormones on endogenous nuclear RNA polymerase I and II in the immature rat uterus. All three compounds caused a rapid elevation in polymerase II activity that reached a peak by the first hour and declined to almost control levels by 2 h after the injection. This transient peak in polymerase II activity was followed by a second elevation by the fourth hour in estradiol- and Nafoxidine-treated animals which was not observed in estriol-treated rats. The activity of polymerase I increased monotonically to very high levels by 4 h and was maintained 12 h or longer in estradiol- and Nafoxidine-treated animals. A similar elevation was observed in estriol-treated rats but the activity declined very rapidly to control levels by 12 h. The second elevation in polymerase II activity and the sustained stimulation of polymerase I activity were correlated with the stimulation of true uterine growth. These data confirm our previous suggestion that long-term nuclear retention of the receptor is a requirement for true uterine growth and suggest that an obligatory response in the production of true growth is the stimulation of a second rise in polymerase II activity and an elevated and sustained activity of polymerase I.
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PMID:RNA polymerase activity and uterine growth: Differential stimulation by estradiol, estriol, and nafoxidine. 94 48

Treatment of MCF-7 cells, a human mammary adenocarcinoma cell line, with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (10-7 M) was associated with a time-dependent reduction in the level of estrogen receptor (ER) mRNA (half-life approximately 3 h). In the presence of the RNA synthesis inhibitor actinomycin D [5.0 micrograms/ml (4.0 microM)], half-life of ER mRNA was much longer (approximately 12 h). Furthermore, the TPA-dependent down-regulation of ER mRNA was abolished by actinomycin D. Similar effects were observed with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (150 microM), an inhibitor of RNA polymerase. Inhibition of protein synthesis by cycloheximide (50 microM) or puromycin [50 micrograms/ml (92 microM)] did not alter the steady state level of ER mRNA during a period of 10-12 h. Furthermore, these inhibitors of protein synthesis did not prevent the down-regulation of ER mRNA in the presence of TPA. Our studies show that degradation of ER mRNA by TPA in MCF-7 cells is dependent on ongoing RNA synthesis but not on protein synthesis. This indicates that an RNA molecule with rapid turnover, which does not require translation, might be involved in the TPA-dependent ER mRNA decay.
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PMID:Down-regulation of messenger ribonucleic acid (mRNA) for the estrogen receptor (ER) by phorbol ester requires ongoing RNA synthesis but not protein synthesis. Is hormonal control of ER mRNA degradation mediated by an RNA molecule? 138 61

The ability of the c-Jun protein, the main component of the transcription factor AP1, to interact directly or indirectly with the RNA polymerase II-initiation complex to activate transcription was investigated by in vivo transcription interference ("squelching") experiments. Coexpression of a Jun mutant lacking its DNA binding domain strongly represses the activity of wild-type c-Jun. Repression depends on the presence of the transactivation domains (TADs), suggesting that a limiting factor interacting with the TADs is essential to link Jun and the components of the transcriptional machinery. The activity of this intermediary factor(s) is restricted to TADs characterized by an abundance of negatively charged amino acids, as demonstrated by the abilities of the TADs of JunB, GAL4, and VP16 to repress c-Jun activity. Depending on the presence of the TADs of Jun, we found physical interaction between Jun and a cluster of three proteins with molecular masses of 52, 53, and 54 kDa (p52/54). Association between Jun and p52/54 is strongly reduced in the presence of VP16, suggesting that the two proteins compete for binding to p52/54. Transcription factors containing a different type of TAD (e.g., GHF1, estrogen receptor, or serum response factor) fail to inhibit Jun activity, suggesting that these proteins act through a different mechanism. We consider the requirement of Jun to interact with p52/54 utilized by other transcription factors a new mechanism in the regulation of transcription of Jun-dependent target genes.
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PMID:A common intermediary factor (p52/54) recognizing "acidic blob"-type domains is required for transcriptional activation by the Jun proteins. 144 82


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