Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen administration to male Xenopus causes the cytoplasmic destabilization of the hepatic serum protein coding mRNAs, most notably, albumin, yet has little effect on mRNAs encoding intracellular proteins such as ferritin. This report describes an estrogen-inducible ribonuclease activity found in liver polysomes that degrades albumin mRNA 4 times faster in vitro than it degrades ferritin mRNA. This differential rate of degradation was observed upon incubation of polysome extract with free liver RNA, isolated liver mRNPs, or transcripts from plasmid vectors. A cleavage fragment consisting of a doublet of approximately 194 nucleotides in length was consistently observed upon digestion of transcripts for the full length or 5' half of albumin mRNA. The generation of this cleavage fragment was used as an assay to study properties of the polysome nuclease activity. The 194 doublet is produced by the action of a Mg(2+)-independent endonuclease. This distinguishes the Xenopus liver enzyme from the enzymes that degrade histone or c-myc mRNA in vitro. It is inactivated by 400 mM NaCl or heating at 90 degrees C, but not by placental ribonuclease inhibitor or N-ethylmaleimide. Finally, the polysomal nuclease activity does not degrade double-stranded RNA. We believe the estrogen-induced nuclease activity contains an enzyme(s) that may mediate hormone-regulated changes in mRNA stability in this tissue.
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PMID:Estrogen-induced ribonuclease activity in Xenopus liver. 193 72

Estrogen receptors (ER) from rat and rabbit uterine cytosol were examined for their sensitivity to ribonuclease (RNase). After RNase treatment, a major part of rabbit uterine ER was converted from the 7S to 3-4S form, and its binding to DNA-cellulose was increased by 40%. Similar treatment on rat uterine ER showed a shift from 7S to 4.5S, and the DNA-cellulose binding was stimulated by 20%. Measurement of endogenous RNase levels showed that lower RNase concentration in rabbit uterine cytosol coincided with larger stimulation of DNA-cellulose binding by exogenous RNase. These results indicate that a major part of 7S ER is susceptible to RNase, and cleavage of bound RNA seems to uncover additional binding sites for DNA. In contrast to the general thinking that 4S to 5S transformation is essential for nuclear binding, we have observed that RNase-treated rat uterine ER did not undergo such a transformation by warming at 25 degrees C, while DNA-cellulose binding of the receptors increased. Thus, temperature activation could occur independent of 4S to 5S transformation.
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PMID:Effect of ribonuclease on the physico-chemical properties of estrogen receptor. 241 Jun 67

Previous experiments have demonstrated that C-type natriuretic peptide (CNP) expression in the uterus varies during the estrous cycle with maximal expression at proestrus. The present study was designed to determine whether exogenous steroid hormones regulate uterine CNP expression in ovariectomized mice. Estradiol increased significantly (3-fold) uterine immunoreactive CNP (irCNP) rapidly and dose dependently in ovariectomized mice as measured by radioimmunoassay. Other steroids produced either no significant change (testosterone, 1 mg; 2-methoxyestradiol, 1 microgram) or weak induction (estriol, 1 microgram) from vehicle controls. Progesterone (1 mg) significantly attenuated the estrogen-stimulated irCNP response by 50% when injected 30 min before estrogen (1 microgram) in estrogen-primed ovariectomized mice. Estrogen-stimulated increases in uterine CNP transcripts detected by ribonuclease protection analyses were blocked by actinomycin D (160 micrograms) or ICI-164,384 (20 micrograms), a specific nuclear estrogen receptor antagonist. These results indicate that a nuclear estrogen receptor is required for estrogen to stimulate uterine CNP transcription and that progesterone negatively regulates estrogen-stimulated CNP expression.
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PMID:Estradiol induces C-type natriuretic peptide gene expression in mouse uterus. 943 3

The aim of this study was to characterize the effect of estrogen on the expression of neuronal and endothelial isoforms of nitric oxide (NO) synthase (NOS) in myometrium, endometrium, and caruncle (nonglandular endometrium) in nonpregnant sheep. Twenty sheep were castrated during synchronized estrus (Days 14-16) and 4 days after surgery treated i.v. through the jugular with 100 microg/day of estradiol-17beta for 5 (n = 6) or 8 (n = 6) days or with vehicle (n = 8). Nitric oxide synthase mRNA was measured by ribonuclease protection assay, and NOS protein mass was measured by Western immunoblotting. Data were analyzed by ANOVA and Tukey's test. The three distinct uterine compartments studied contained the mRNA and protein for the neuronal (type I NOS) and the endothelial (type III NOS) isoforms of NOS. However, no inducible NOS was detected. Estrogen exhibited a differential effect on NOS expression in a tissue compartment- and NOS isoform-specific manner. In myometrium and caruncles, but not in endometrium, type I NOS mRNA and protein mass increased significantly (p < 0.05) after 5 or 8 days of estrogen. In contrast, type III NOS increased significantly in myometrium only after 8 days, whereas in endometrium and caruncles the increase was significant in the 5-day treatment group (p < 0.05). We conclude that the expression of type I NOS and type III NOS in the uterus are differentially regulated by estrogen. This differential regulation suggests that the NO produced within the uterus serves more than one physiological role. In myometrium it may be a uterorelaxant and regulate glucose utilization, and in endometrium and myometrium it may regulate blood flow.
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PMID:Nonpregnant sheep uterine type I and type III nitric oxide synthase expression is differentially regulated by estrogen. 1020 84

Estrogen induces a global change in the translation profile of Xenopus hepatocytes, replacing serum protein synthesis with production of the yolk protein precursor vitellogenin. This is accomplished by the coordinate destabilization of serum protein mRNAs and the transcriptional induction and subsequent stabilization of vitellogenin mRNA. Previous work identified an endonuclease activity whose appearance on polysomes correlated with the disappearance of serum protein mRNAs. This enzyme, polysomal ribonuclease 1 (PMR1), is a novel member of the peroxidase gene family. The current study examined the association of PMR1 with its mRNA targets on polysomes and mRNPs. The highest amount of polysome-bound PMR1 was observed prior to estrogen induction of mRNA decay. Its distribution on sucrose density gradients matched the absorbance profile of polysome-bound mRNA, suggesting that PMR1 forms a latent complex with mRNA. Following dissociation with EDTA the 62 kDa PMR1 sedimented with a larger complex of >670 kDa. Estrogen induces a 22-fold increase in unit enzymatic activity of polysome-bound PMR1, and a time-dependent loss of PMR1 from polysomes in a manner that mirrors the disappearance of albumin mRNA. These data suggest that the key step in the extensive estrogen-induced change in mRNA decay in Xenopus liver is activation of a latent mRNA endonuclease associated with its target mRNA.
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PMID:Polysomal ribonuclease 1 exists in a latent form on polysomes prior to estrogen activation of mRNA decay. 1122 65

Resistance to hormonal therapy is often a problem in the treatment of breast cancer patients. It has been suggested that resistance could be explained by altered nuclear hormone receptor or coregulator levels or inappropriately increased agonist activity of selective estrogen receptor modulator (SERM). To test these hypotheses, we have established novel MCF-7 cell line-derived in vitro models of anti-estrogen- and progestin-resistant and estrogen-independent breast cancer by long-term culture in the presence of toremifene and medroxyprogesterone acetate (MPA) and in the absence of estradiol, respectively. Using cell growth and multiprobe ribonuclease protection assays, the expression of 5 nuclear hormone receptors and 9 coregulators as well as the alterations in the cell proliferation and target gene transcription in response to hormonal treatments were studied. Progesterone receptor (PR) expression was decreased and silencing mediator for retinoid acid and thyroid hormone receptors (SMRT) and amplified in breast cancer-1 (AIB1) expression increased in anti-estrogen-resistant cells. Estrogen caused PR and ERbeta upregulation in all cell lines, but we did not observe increased agonist activity of anti-estrogen measured by regulation of these estrogen target genes. Basal ERalpha levels and estrogenic growth response were decreased and p300/CBP-associated factor (pCAF) and AIB1 upregulated by estrogen in progestin-resistant cells, but coregulator levels were unchanged. Estrogen-independent cells were still estrogen-responsive and PR, nuclear receptor corepressor (N-CoR) and SMRT expression was increased whereas steroid receptor coactivator-1 (SRC-1a) and CBP-related protein p300 (p300) expression decreased. Their growth was inhibited by toremifene, but estradiol was able to abrogate this effect, which might have interesting clinical implications concerning the use of postmenopausal hormone replacement therapy.
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PMID:Steroid hormone receptors and coregulators in endocrine-resistant and estrogen-independent breast cancer cells. 1615 93