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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genes whose expression is growth factor regulated are likely to be important components in the mechanisms controlling cell proliferation and differentiation. With the aim of identifying some of those genes, a lambda cDNA library was prepared with poly(A)+ RNA from quiescent NIH 3T3 cells stimulated with serum for 4 h in the presence of cycloheximide. Differential screening of approximately 200,000 recombinant phage plaques revealed 2,540 clones that cross hybridized preferentially with [32P]cDNA derived from RNA of stimulated cells rather than with cDNA derived from nonstimulated cells. Cross hybridization of these clones identified 82 independent sequences, including c-fos and c-myc. Seventy-one clones were further studied. Analysis of the changes in transcription and mRNA levels after serum stimulation demonstrated that the kinetics and extent of the induction vary dramatically between the different genes. Cycloheximide in all cases superinduced the mRNA levels by two mechanisms, inhibiting the shutoff of transcription and prolonging the half-lives of the mRNAs. Our results showed that induction of proliferation is accompanied by the onset of a complex genetic program.
Mol Cell Biol 1988 May
PMID:Complexity of the early genetic response to growth factors in mouse fibroblasts. 289 31

Acutely isolated rat adipocytes have been maintained in primary culture for several days and the effects of culture on the kinetics of 125I-human growth hormone (hGH) binding to adipocytes have been determined. A marked increase (500-1000%) in specific binding of 125I-hGH was observed over the first 3 days of culture--acutely isolated adipocytes (5.5 +/- 1.4%, mean +/- SE, n = 47) compared to 3-day cultured adipocytes (48 +/- 7%, mean +/- SE, n = 8). Specific binding of 125I-hGH to both acutely isolated and cultured adipocytes was dependent on incubation time and temperature (equilibrium being reached in 1 h at 37 degrees C and 2 h at 22 degrees C). Binding was reversible (t1/2 approximately 1.5 h). Scatchard analysis revealed linear plots and showed that the increase in binding during culture was due to an increase in the number of receptors per cell (approximately 20 000 to approximately 170 000) with little or no change in binding affinity (Ka approximately 1 X 10(9) M-1). Cycloheximide inhibited the increase in binding sites during culture suggesting a requirement for de novo protein synthesis. Addition of unlabelled hGH to the culture medium resulted in a marked down-regulation of the GH receptor by 2 days. The GH-induced decrease in receptor number was to due to receptor occupancy by exogenously added GH. The studies to date indicate that the cultured rat adipocyte should provide a useful model for a comprehensive study of the cellular mechanisms and dynamics of GH receptor regulation.
Mol Cell Endocrinol 1986 Sep
PMID:Growth hormone receptors in cultured adipocytes: a model to study receptor regulation. 301 89

The effects of inhibin on gonadotropin secretion from cultured rat anterior pituitary cells were examined by using purified porcine follicular fluid (pFF) 32 kDa inhibin. pFF 32 kDa inhibin suppressed the basal FSH secretion as well as cell content of FSH with identical ED50 values (ED50 = 1.0 ng/ml) in a dose-dependent manner, but did not alter either basal secretion or cell content of LH. On the other hand, pretreatment of the pituitary cells with pFF 32 kDa inhibin during the first 3 days resulted in suppression of subsequent LH-RH-stimulated release of both FSH and LH in a dose-dependent manner, indicating that the suppression of LH-RH-stimulated release of LH is one of the intrinsic inhibin actions on pituitary cells. The marked difference between ED50 values for FSH (ED50 = 1.1 ng/ml) and LH (ED50 = 2.5 ng/ml) in the suppression of LH-RH-stimulated release of gonadotropins, together with the fact that the total amount of LH (cell content plus released) after LH-RH stimulation remained unchanged following inhibin treatment suggests that the suppression of LH-RH-stimulated release of LH by inhibin is quite different from that of FSH regarding the action mechanism. Similarly, cycloheximide, an inhibitor of protein biosynthesis, suppressed both basal secretion and cell content of FSH with almost the same ED50 values (ED50 = 22.5 ng/ml) but did not alter either basal secretion or cell content of LH. Cycloheximide also suppressed LH-RH-stimulated release of both FSH and LH, and the ED50 values were different from each other (ED50 = 25.0 ng/ml for FSH and 60.0 ng/ml for LH suppression, respectively). Our finding that cycloheximide completely mimicked the action of inhibin on gonadotropin secretion strongly suggests that LH is quite insensitive to biosynthetic inhibition, and that preferential effects of inhibin or cycloheximide on FSH in appearance may reflect the difference between LH and FSH in susceptibility to biosynthetic inhibition.
Mol Cell Endocrinol 1987 May
PMID:Action mechanism of inhibin in vitro--cycloheximide mimics inhibin actions on pituitary cells. 303 24

Insulin alone at concentrations of less than 1 to 5 uU/ml increased the enzyme activities of glycogen synthase, synthase phosphatase, phosphorylase, and phosphorylase phosphatase in hepatoma H4 cells in culture in the presence and absence of serum. Increase in total and active forms of glycogen synthase and phosphorylase were observed. Cycloheximide blocked the action of insulin on glycogen synthase, glycogen synthase phosphatase and phosphorylase phosphatase. The enzymes with the exception of glycogen synthase phosphatase were expressed with greater hormonal sensitivity in the absence as compared to the presence of serum in terms of hormone concentration required and or time of onset. These results demonstrate that these glycogen metabolizing enzymes are under long term control by insulin, with glycogen synthase being the most sensitive of the enzymes studied to the action of the hormone.
Mol Cell Biochem 1987 Jun
PMID:Long term regulation of glycogen metabolizing enzymes by insulin in H4 hepatoma cells. 304 Dec

Dexamethasone increases type 1 plasminogen activator inhibitor (PAI-1) activity released from the human fibrosarcoma cell line HT-1080. We demonstrated that dexamethasone caused about 10-fold increases in the intracellular and extracellular levels of PAI-1 protein, as measured by an enzyme-linked immunosorbent assay, in the rate of PAI-1 biosynthesis, and in the PAI-1 mRNA level. The effects on PAI-1 biosynthesis and mRNA level were detectable within 4 h and were maximal 16 to 24 h after the addition of dexamethasone. Cycloheximide did not inhibit the dexamethasone-induced increases in the capacity of the cells to synthesize PAI-1 and in the PAI-1 mRNA level.
Mol Cell Biol 1987 Aug
PMID:Plasminogen activator inhibitor type 1 biosynthesis and mRNA level are increased by dexamethasone in human fibrosarcoma cells. 311 90

Several known inducers of the heat shock response (heat stress, arsenite, and heavy metals) were shown to cause a significant elevation of c-fos mRNA in HeLa cells. Heat stress resulted in a time- and temperature-dependent prolonged elevation in the level of c-fos mRNA, which was accompanied by increased translation of c-fos protein and its appearance in the nucleus. Elevated expression of c-fos during heat stress was paralleled by induction of hsp 70 mRNA, while levels of c-myc and metallothionein mRNAs declined. Treatment of HeLa cells with arsenite or heavy metals also resulted in increased levels of hsp 70, as well as c-fos mRNA. Although elevated expression of c-fos was prevented by inhibitors of RNA synthesis, analysis of relative rates of gene transcription showed that during heat stress there was a negligible change in c-fos transcription. Therefore, the enhanced expression of c-fos during the heat shock response is likely to occur primarily through posttranscriptional processes. Cycloheximide was also shown to significantly increase the c-fos mRNA level in HeLa cells. There results are consistent with the observation that these inducers of the heat shock response, as well as cycloheximide, repress protein synthesis and suggest that the increase in the level of c-fos mRNA is caused by an inhibition of protein synthesis. This supports the hypothesis that c-fos mRNA is preferentially stabilized under conditions which induce the heat shock response, perhaps by decreased synthesis of a short-lived protein which regulates c-fos mRNA turnover.
Mol Cell Biol 1987 Oct
PMID:The heat shock response in HeLa cells is accompanied by elevated expression of the c-fos proto-oncogene. 331 77

We tested the effects of inhibitors of protein and RNA synthesis on the disaggregation-mediated destabilization of prespore mRNAs in Dictyostelium discoideum. Incubating disaggregated cells with daunomycin to inhibit RNA synthesis prevented the loss of prespore mRNAs, whereas the inhibitor decreased or did not affect levels of the common mRNAs CZ22 and actin. Protein synthesis inhibitors varied in their effects. Cycloheximide, which inhibited protein synthesis almost completely, prevented the loss of the prespore mRNAs, but puromycin, which inhibited protein synthesis less well, did not. These results indicate that the process of specific mRNA destabilization requires the synthesis of RNA and possibly of protein.
Mol Cell Biol 1987 Dec
PMID:Specific mRNA destabilization in Dictyostelium discoideum requires RNA synthesis. 343 99

Protein synthesis in intact Plasmodium falciparum was 333 times more sensitive to cycloheximide than to chloramphenicol. The 50% inhibitory concentration (IC50) of cycloheximide in a 27-h assay in vitro was 6 X 10(-7) M but no constant cycloheximide-insensitive fraction of total protein synthesis was observed at concentrations of this inhibitor between 10(-7) and 10(-2) M. 0.24% of total protein synthesis occurred in the presence of 10(-3) M cycloheximide but the chloramphenicol sensitivity of this fraction was similar to that of overall protein synthesis (IC50 2 X 10(-4) M). The major fraction of protein synthesis by P. falciparum, therefore, is assumed to be cytoplasmic and to occur on 80S ribosomes. Cycloheximide-insensitive, chloramphenicol-sensitive (70S ribosomal) protein synthesis being undetectable by the methods employed, mitochondrial protein synthesis in P. falciparum is presumed to constitute a considerably smaller fraction of the total protein synthetic capacity than observed in other lower eukaryotes.
Mol Biochem Parasitol 1986 Jan
PMID:Mitochondrial protein synthesis in Plasmodium falciparum. 351 75

The relative decay of four human messenger RNAs, gamma globin, delta globin, c-myc and H4 histone, were compared in a cell-free system. Under appropriate conditions, they are degraded in vitro in approximately the same relative order as in vivo: histone faster than c-myc and delta globin faster than gamma globin. Degradation of polysome-associated H4 histone mRNA and of deproteinized histone mRNA begins at or near the 3' terminus. At least a portion of the mRNA then continues to be degraded in a 3' to 5' direction. Discrete 3'-terminal degradation hold-up points are observed, suggesting that 3' to 5' degradation occurs non-uniformly. Cycloheximide and puromycin inhibit protein synthesis but do not affect the rate or directionality of histone mRNA decay in vitro. We conclude that the rate-limiting step in H4 histone mRNA decay occurs at or near the 3' terminus and that at least a portion of the mRNA molecule is subsequently degraded 3' to 5', probably via a processive exonuclease.
J Mol Biol 1986 Apr 20
PMID:H4 histone messenger RNA decay in cell-free extracts initiates at or near the 3' terminus and proceeds 3' to 5'. 352 49

Six cDNA clones have been identified that are complementary to transcripts present in young zygotes of Chlamydomonas reinhardtii but absent from vegetative and gametic cells. Five early transcripts are synthesized within 5 to 10 min of fertilization; the sixth, late, transcript is not synthesized until 90 min following fertilization. Synthesis of both classes requires cell fusion between gametes. Cycloheximide fails to inhibit early mRNA synthesis, indicating that transcription factors must preexist in the gametes and be activated by cytoplasmic confluence. By contrast, cycloheximide blocks synthesis of the late transcript, suggesting that an early protein product(s) is required for expression of the late gene. Restriction fragment length polymorphism analysis of inter- and intraspecific genetic crosses demonstrates that one of the early genes is very tightly linked to the mating-type locus.
Mol Cell Biol 1987 Jul
PMID:Transcription of novel genes, including a gene linked to the mating-type locus, induced by Chlamydomonas fertilization. 361 94


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