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)

Glutaminase mRNA levels increased over 3-fold relative to total RNA, poly(A)+ RNA, and beta-actin mRNA in neonatal rat cerebellar granule cells as the cells differentiated between days 3 and 8 in culture. In contrast, mRNA levels of another glutamate cycle enzyme, glutamine synthetase, remained constant. Glutaminase protein levels increased per cell more than 2-fold between days 3 and 8, and at least 3-fold by day 10 in these cells. The total amount of glutamate per cell increased about 40% during this period. Glutaminase induction paralleled the development of Ca2+-dependent glutamate release, and the formation of neurites, synaptic vesicles, and synapses. The induction of glutaminase in developing granule cells is consistent with a special role for glutaminase in the synthesis of neurotransmitter glutamate.
Brain Res Mol Brain Res 1989 Jul
PMID:Developmental induction of glutaminase in primary cultures of cerebellar granule cells. 257 Mar 41

The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers.
Mol Cell Biol 1989 Oct
PMID:Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. 257 31

The effect of DNA damage induced by the carcinogen chromium(VI) on the function of DNA as a template for transcription of constitutive and inducible genes was examined in chick embryo liver in vivo. Changes in gene expression, determined using solution hybridization and northern blot analyses to measure steady-state mRNA levels and a nuclear run-off assay to measure gene transcription rates, were compared to chromium-DNA binding and to chromium(VI)-induced DNA damage as previously measured by DNA alkaline elution. Chromium(VI) treatment had little or no effect on either the steady-state mRNA levels or the transcription rates of the constitutively expressed genes for albumin, conalbumin (avian transferrin), or beta-actin. In contrast, chromium(VI) treatment had significant but opposite effects on the basal and drug-inducible expression of 5-aminolevulinate synthase and cytochrome PB1 P450. The changes in steady-state expression of these two inducible genes were similar to the changes in transcription rate, indicating that the effects of chromium were principally transcriptional. Chromium(VI) treatment increased the basal expression of both inducible genes four- to fivefold at maximum, and the time course of this effect was similar to the time course for chromium(VI)-induced DNA damage and repair. In contrast, chromium(VI) pretreatment suppressed by 60-70% at maximum the subsequent induction of these genes by glutethimide, a phenobarbital analog, and the time course of this effect also corresponded to that of chromium(VI)-induced DNA damage and repair. The time courses of the changes in expression of these genes were bimodal, with the second peak corresponding closely to that of chromium(VI)-induced DNA cross-links. However, the first peak occurred during a period when no DNA cross-links or strand breaks were detectable by alkaline elution, although significant levels of chromium were bound to DNA. This suggests that chromium(VI), like cisplatin, may initially produce a DNA monoadduct that subsequently leads to DNA cross-link formation and that both types of chromium(VI)-induced lesions have a significant effect on the expression of targeted genes.
Mol Carcinog 1989
PMID:Differential effects of chromium(VI) on constitutive and inducible gene expression in chick embryo liver in vivo and correlation with chromium(VI)-induced DNA damage. 260 65

We analysed the distribution of actin mRNA in intestinal epithelial cells using in situ hybridization of 35S-labelled cytoplasmic beta-actin RNA. We found that the distribution of actin mRNA generally parallels that of polymerized actin, i.e. there is an accumulation of actin mRNA in the apical end of villous epithelial cells. Furthermore, the development of this asymmetric localization of actin mRNA appears to parallel the elaboration of the cytoskeleton during cellular differentiation. We discuss the possibility that the interaction between actin and its mRNA may be important for the establishment and maintenance of cytoskeletal pattern in polarized epithelial cells.
J Mol Biol 1989 Dec 05
PMID:Asymmetric distribution of actin mRNA and cytoskeletal pattern generation in polarized epithelial cells. 261 33

The role of ongoing protein synthesis in mediating the posttranscriptional effects of hormones on casein gene expression in the COMMA D mouse mammary epithelial cell line was investigated using the protein synthesis inhibitors, cycloheximide and anisomycin. When COMMA D cells were pretreated with insulin and PRL for 24 h, the addition of glucocorticoids induced a greater than 20-fold increase in beta-casein mRNA accumulation with an apparent lag of greater than 8 h. Addition of cycloheximide and anisomycin not only prevented this increase, but unexpectedly, resulted in the rapid disappearance of preexisting beta-casein mRNA with a half-life of approximately 2 h. Under the same conditions, the levels of beta-actin and histone H4 mRNAs were increased markedly. In contrast, when cells were pretreated with all three lactogenic hormones for 48 h before the addition of either protein synthesis inhibitors or actinomycin D, the effects of these inhibitors on the levels of beta-casein mRNA were greatly diminished. This differential sensitivity of beta-casein mRNA to protein synthesis inhibitors was observed only in cells pretreated for greater than 24 h with all three hormones. Experiments performed in the absence of inhibitors indicated that beta-casein mRNA has a long half-life even after hormone withdrawal. These results suggest that hormone-dependent stabilization of cytoplasmic beta-casein mRNA requires ongoing protein synthesis. Cells cultured in the presence of all three lactogenic hormones slowly accumulate a labile protein(s), which exerts a selective effect on casein mRNA stability.
Mol Endocrinol 1989 Dec
PMID:Hormone-dependent beta-casein mRNA stabilization requires ongoing protein synthesis. 262 32

The addition of TSH to FRTL-5 thyroid cells induces a 7- to 8-fold increase in the steady state level of malic enzyme [L-malate-NADP+ oxidoreductase (decarboxylating); EC 1.1.1.40] mRNA, but does not alter beta-actin mRNA levels. Insulin alone or together with TSH has no effect on malic enzyme mRNA. The effect of TSH is not the result of thyroid hormone formation, since the addition of T3 in the presence or in the absence of TSH and the addition of 5% serum (which includes T3 and T4) have no effect. Forskolin (10(-6) M) reproduces the TSH effect, suggesting that cAMP is involved.
Mol Endocrinol 1989 Mar
PMID:Thyrotropin increases malic enzyme messenger ribonucleic acid levels in rat FRTL-5 thyroid cells. 266 74

The accumulation of the cytoskeletal beta- and gamma-actin mRNAs was determined in a variety of mouse tissues and organs. The beta-isoform is always expressed in excess of the gamma-isoform. However, the molar ratio of beta- to gamma-actin mRNA varies from 1.7 in kidney and testis to 12 in sarcomeric muscle to 114 in liver. We conclude that, whereas the cytoskeletal beta- and gamma-actins are truly coexpressed, their mRNA levels are subject to differential regulation between different cell types. The human gamma-actin gene has been cloned and sequenced, and its chromosome location has been determined. The gene is located on human chromosome 17, unlike beta-actin which is on chromosome 7. Thus, if these genes are also unlinked in the mouse, the coexpression of the beta- and gamma-actin genes in rodent tissues cannot be determined by gene linkage. Comparison of the human beta- and gamma-actin genes reveals that noncoding sequences in the 5'-flanking region and in intron III have been conserved since the duplication that gave rise to these two genes. In contrast, there are sequences in intron III and the 3'-untranslated region which are not present in the beta-actin gene but are conserved between the human gamma-actin and the Xenopus borealis type 1 actin genes. Such conserved noncoding sequences may contribute to the coexpression of beta- and gamma-actin or to the unique regulation and function of the gamma-actin gene. Finally, we demonstrate that the human gamma-actin gene is expressed after introduction into mouse L cells and C2 myoblasts and that, upon fusion of C2 cells to form myotubes, the human gamma-actin gene is appropriately regulated.
Mol Cell Biol 1988 Apr
PMID:Structure, chromosome location, and expression of the human gamma-actin gene: differential evolution, location, and expression of the cytoskeletal beta- and gamma-actin genes. 283 53

CAD codes for a trifunctional protein involved in the catalysis of the first three enzymatic activities in the de novo pyrimidine biosynthetic pathway, namely, carbamoyl-phosphate synthetase II (EC 6.3.5.5), aspartate transcarbamylase (EC 2.1.3.2), and dihydroorotase (EC 3.5.2.3). CAD regulation was studied in the human promyelocyte leukemic line HL-60 as it differentiated into monocytic or granulocytic lineages after induction by 12-O-tetradecanoylphorbol-13-acetate or trans-retinoic acid and dibutyryl cyclic AMP, respectively. Within 12 h of induction of HL-60 cells with either inducer, total cellular levels of CAD RNA essentially disappeared. On the other hand, no apparent decreases in beta-actin RNA levels were seen even 48 h after HL-60 cells were induced, as compared with untreated cells. With nuclear runoff assays, it was clearly shown that the inactivation of CAD gene expression during the induction of HL-60 cells with either inducer was at the transcriptional level. The nuclear runoff experiments also demonstrated that the CAD gene expression was shut down in less than 4 h after induction, well before morphological changes were observed in these cells. At the enzymatic level, the activity of aspartate transcarbamylase, one of the three enzymes encoded by the CAD gene, decreased by about half within 24 h of induction, suggesting a CAD protein half-life of 24 h in differentiating HL-60 cells. Nevertheless, this means that significant levels of aspartate transcarbamylase activity remained even after the cells have stopped proliferating. From the RNA data, it is clear that CAD gene expression is rapidly turned off as promyelocytes begin to terminally differentiate into macrophages and granulocytes. We suspect that the inactivation of the CAD gene in induced HL-60 cells is a consequence of the differentiating cells leaving the cell cycle and becoming nonproliferating.
Mol Cell Biol 1987 May
PMID:Transcriptional regulation of the human CAD gene during myeloid differentiation. 288 43

The complete nucleotide sequence of a genomic clone encoding the mouse skeletal alpha-actin gene has been determined. This single-copy gene codes for a protein identical in primary sequence to the rabbit skeletal alpha-actin. It has a large intron in the 5'-untranslated region 12 nucleotides upstream from the initiator ATG and five small introns in the coding region at codons specifying amino acids 41/42, 150, 204, 267, and 327/328. These intron positions are identical to those for the corresponding genes of chickens and rats. Similar to other skeletal alpha-actin genes, the nucleotide sequence codes for two amino acids, Met-Cys, preceding the known N-terminal Asp of the mature protein. Comparison of the nucleotide sequences of rat, mouse, chicken, and human skeletal muscle alpha-actin genes reveals conserved sequences (some not previously noted) outside of the protein-coding region. Furthermore, several inverted repeat sequences, partially within these conserved regions, have been identified. These sequences are not present in the vertebrate cytoskeletal beta-actin genes. The strong conservation of the inverted repeat sequences suggests that they may have a role in the tissue-specific expression of skeletal alpha-actin genes.
Mol Cell Biol 1986 Jan
PMID:The complete sequence of the mouse skeletal alpha-actin gene reveals several conserved and inverted repeat sequences outside of the protein-coding region. 302 20

The development of a non-competitive, solid-phase radioimmunoassay for quantitating anti-actin antibody is described. Anti-actin antibody was captured on BSA-coated microspheres of polystyrene to which a synthetic peptide representing the fifteen amino acid N-terminus of human beta-actin was covalently attached. A rabbit antiserum against the actin peptide fragment was used as reference serum for the assay. Serums of 23 out of 28 (82%) patients with chronic active hepatitis, shown to have anti-actin antibodies (range 2-140 micrograms ml-1) by immunofluorescence and immunoblot assays, were used to validate the radioimmunoassay. Only 7 out of 130 (5%) control subjects exhibited anti-actin antibody serum concentrations above 14 micrograms ml-1 (range 2-20 micrograms ml-1), the 95% confidence interval. Anti-actin antibody serum concentrations were determined to be elevated in 28 out of 47 (60%) patients with juvenile rheumatoid arthritis (range 5-89 micrograms ml-1), 43 out of 64 (67%) patients with human immunodeficiency virus infection and AIDS (range 3-80 micrograms ml-1), and 17 out of 23 (74%) infants with Kawasaki Syndrome (range 7-138 micrograms ml-1). All of the differences observed between patient groups, either singly or collectively, and the control group are highly significant (P less than 0.001) as judged by chi-square analysis. Since all of these disease states contain elements of viral infection and autoimmune disease, it is possible that viral infection in these diseases triggers the production of anti-actin antibody, possibly by means of molecular mimicry in response to viral oncogenes or to abnormal expression of actin in host tissue. This radioimmunoassay for anti-actin antibodies may prove to be a useful tool for the detection and monitoring of certain forms of autoimmune disease.
Mol Cell Probes 1988 Dec
PMID:Radioimmunoassay for anti-actin antibody: application in viral and autoimmune diseases. 307 13


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