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)

Estradiol is likely involved in stimulating developmental changes in the ability of the rat pituitary to secrete prolactin. To investigate the possibility that these changes involve proliferation of prolactin cells, estradiol effects on pituitary growth and prolactin synthesis were examined. Estradiol treatment of immature female rats stimulates increases in pituitary weight, [3H] thymidine incorporation, DNA content and prolactin synthesis. Treatment of rats with the DNA synthesis inhibitor, hydroxyurea, partially blocked the ability of estradiol to stimulate prolactin synthesis suggesting that at least part of the effect of estrogen is due to cell proliferation. These results suggest that estrogen-induced proliferation of prolactin cells is involved in the developmental processes of the pituitary.
Mol Cell Endocrinol 1979 Mar
PMID:Estrogen-induced prolactin and DNA synthesis in immature female rat pituitaries. 44 85

A DNA-binding protein has been identified from extracts of the budding yeast Saccharomyces cerevisiae which binds to sites present in the promoter regions of a number of yeast genes transcribed by RNA polymerase II, including SIN3 (also known as SDI1), SWI5, CDC9, and TOP1. This protein also binds to a site present in the enhancer for the 35S rRNA gene, which is transcribed by RNA polymerase I, and appears to be identical to the previously described REB1 protein (B. E. Morrow, S. P. Johnson, and J. R. Warner, J. Biol. Chem. 264:9061-9068, 1989). When oligonucleotides containing a REB1-binding site are placed between the CYC1 upstream activating sequence and TATA box, transcription by RNA polymerase II in vivo is substantially reduced, suggesting that REB1 acts as a repressor of RNA polymerase II transcription. The in vitro levels of the REB1 DNA-binding activity are reduced in extracts prepared from strains bearing a mutation in the SIN3 gene. A greater reduction in REB1 activity is observed if the sin3 mutant strain is grown in media containing galactose as a carbon source.
Mol Cell Biol 1990 Apr
PMID:Identification of a Saccharomyces cerevisiae DNA-binding protein involved in transcriptional regulation. 218 Dec 83

The SIN3 gene (also known as SDI1) is a negative regulator of the yeast HO gene. Mutations in SIN3 suppress the requirement for the SWI5 activator for expression of the yeast HO gene and change the normal asymmetric pattern of HO expression in mother and daughter cells. Furthermore, the in vitro DNA-binding activity of several DNA-binding proteins is reduced in extracts prepared from sin3 mutants. We have cloned the SIN3 gene and determined that a haploid strain with a SIN3 gene disruption is viable. We determined the sequence of the SIN3 gene, which is predicted to encode a 175-kDa polypeptide with four paired amphipathic helix motifs. These motifs have been identified in the myc family of helix-loop-helix DNA-binding proteins and in the TPR family of regulatory proteins. The SIN3 transcript was mapped, and it was determined that the SIN3 transcript was absent in stationary-phase cells. Immunofluorescence microscopy with anti-SIN3 antibody demonstrated that SIN3 protein was present in nuclei. A comparison of restriction map and sequence data revealed that SIN3 is the same as regulatory genes UME4 and RPD1.
Mol Cell Biol 1990 Nov
PMID:The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. 223 25

The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also mediates the DNA cleavage activity and cytotoxicity of clinically important anticancer agents such as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent BALB/c 3T3 cells following serum stimulation. Etoposide-mediated DNA break frequency in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by immunoblotting. Density-arrested A31 cells exhibited a much lower sensitivity to the effects of etoposide than did actively proliferating cells. Upon serum stimulation of the quiescent cells, however, there was a marked increase in drug sensitivity which began during S phase and reached its peak just before mitosis. Maximal drug sensitivity during this period was 2.5 times greater than that of log-phase cells. This increase in drug sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 h of exposure of cells to the protein synthesis inhibitor cycloheximide, but the DNA synthesis inhibitor aphidicolin had no effect. In contrast to the sensitivity of cells to drug-induced DNA cleavage, maximal cytotoxicity occurred during S phase. A 3-h exposure to cycloheximide before etoposide treatment resulted in nearly complete loss of cytotoxicity. Our findings indicate that topoisomerase II activity fluctuates with cell cycle progression, with peak activity occurring during the G2 phase. This increase in topoisomerase II is protein synthesis dependent and may reflect a high rate of enzyme turnover. The dissociation between maximal drug-induced DNA cleavage and cytotoxicity indicates that the topoisomerase-mediated DNA breaks may be necessary but are not sufficient for cytotoxicity and that the other factors which are particularly expressed during S phase may be important as well.
Mol Cell Biol 1987 Sep
PMID:Topoisomerase-specific drug sensitivity in relation to cell cycle progression. 282 20

The kinetics of mating type switching in Saccharomyces cerevisiae can be followed at the DNA level by using a galactose-inducible HO (GAL-HO) gene to initiate the event in synchronously growing cells. From the time that HO endonuclease cleaves MAT a until the detection of MAT alpha DNA took 60 min. When unbudded G1-phase cells were induced, switched to the opposite mating type in "pairs." In the presence of the DNA synthesis inhibitor hydroxyurea, HO-induced cleavage occurred but cells failed to complete switching. In these blocked cells, the HO-cut ends of MATa remained stable for at least 3 h. Upon removal of hydroxyurea, the cells completed the switch in approximately 1 h. The same kinetics of MAT switching were also seen in asynchronous cultures and when synchronously growing cells were induced at different times of the cell cycle. Thus, the only restriction that confined normal homothallic switching to the G1 phase of the cell cycle was the expression of HO endonuclease. Further evidence that galactose-induced cells can switch in the G2 phase of the cell cycle was the observation that these cells did not always switch in pairs. This suggests that two chromatids, both cleaved with HO endonuclease, can interact independently with the donors HML alpha and HMRa.
Mol Cell Biol 1988 Jun
PMID:Physical monitoring of mating type switching in Saccharomyces cerevisiae. 284 79

We used a gene-specific S1 nuclease assay to study the changes in steady-state mRNA levels of several core histone variants during the differentiation of murine erythroleukemia cells. These studies allowed us to distinguish three distinct expression classes of histone genes. The expression of the major replication-dependent class of histone genes was tightly linked to DNA synthesis. The concentrations of these transcripts decreased rapidly as cell division slowed during the process of differentiation. In contrast, the replication-independent H3.3 transcript levels were constitutively maintained throughout differentiation and were unaffected by inhibitors of DNA or protein synthesis. We also identified among the cloned histone genes used as probes a third expression class, the partially replication-dependent variants. Expression of these transcripts became transiently uncoupled from the reduced rate of DNA synthesis accompanying the early stages of differentiation. We show that their synthesis is sensitive to the DNA synthesis inhibitor hydroxyurea but that selective uncoupling from DNA synthesis of these histone mRNAs occurs at a specific stage of differentiation. We present several hypotheses to explain how this might be accomplished. The expression characteristics of the mRNAs studied coincided with those of the proteins for which they code, indicating that changes in the relative levels of the different variants is mediated at least in part by changes in mRNA levels.
Mol Cell Biol 1985 Nov
PMID:Changes in the levels of three different classes of histone mRNA during murine erythroleukemia cell differentiation. 301 84

In this work we have addressed two questions. Does switch recombination occur before membrane expression or only concomitantly with induction to high rate synthesis and secretion of IgG? Does interleukin-4 induce switch to IgG1 or maturation of already switched cells? To answer these questions we used the DNA synthesis inhibitor hydroxyurea (HU) to analyze the requirements for DNA replication in the induction of membrane expression or high rate secretion of all IgG subclasses by cultures of mouse spleen cells stimulated by lipopolysaccharide (LPS) and supplemented with IL-4, the absolute numbers of cells bearing membrane bound IgG was always decreased by HU, indicating that immunoglobulin class switching requires DNA replication. IL-4 did not augment the numbers of cells expressing any IgG isotype. In contrast, the number of high rate secretors of all IgG isotypes was not affected by HU, except in the case of IgG3 and IgG2b shortly after stimulation. Addition of IL-4 resulted in an increased number of secretory cells, and also this effect was resistant to HU. Thus, for any isotype, treatment with HU or IL-4 increased the frequency of secretory cells relative to the surface positive population. This data indicates that: 1) IL-4 is a broad range, non isotype-specific maturation factor for LPS-activated B cells; 2) induction to high rate secretion has a negative effect on proliferation; and 3) immunoglobulin class switch, but not induction to secretion of any immunoglobulin isotype, requires DNA replication, suggesting that switch recombination had to occur before expression of IgG in the membrane-bound form.
J Mol Cell Immunol 1988
PMID:Membrane expression of IgG but not maturation to secretion requires DNA replication. 326 37

The first detectable step in the degradation of human H4 histone mRNA occurs at the 3' terminus in a cell-free mRNA decay system (J. Ross and G. Kobs, J. Mol. Biol. 188:579-593, 1986). Most or all of the remainder of the mRNA is then degraded in a 3'-to-5' direction. The experiments described here were designed to determine whether a similar degradation pathway is followed in whole cells. Two sets of short-lived histone mRNA decay products were detected in logarithmically growing erythroleukemia (K562) cells. These products, designated the -5 and -12 RNAs, were generated by the loss of approximately 4 to 6 and 11 to 13 nucleotides, respectively, from the 3' terminus of histone mRNA. The same decay products were observed after a brief incubation in vitro. They were in low abundance or absent from cells that were not degrading histone mRNA. In contrast, they were readily detectable in cells that degraded the mRNA at an accelerated rate, i.e., in cells cultured with a DNA synthesis inhibitor, either cytosine arabinoside or hydroxyurea. During the initial stages of the decay process, as the 3' terminus of the mRNA was being degraded, the 5'-terminal region remained intact. These results indicate that the first detectable step in human H4 histone mRNA decay occurs at the 3' terminus and that degradation proceeds 3' to 5', both in cells and in cell-free reactions.
Mol Cell Biol 1986 Dec
PMID:Histone mRNA degradation in vivo: the first detectable step occurs at or near the 3' terminus. 346 77

Replication, as measured by virus production, of both the flavivirus Japanese encephalitis virus (JEV) and the alphavirus Venezuelan encephalitis virus (VEV) was unaffected by short pulses of actinomycin D (act D) at early times postinfection (PI). Replication of JEV was found to be partially inhibited by continuous exposure to act D under conditions where VEV replication was equally sensitive to the drug. JEV replication proceeded normally in the presence of mitomycin C, a DNA synthesis inhibitor. Autoradiographic analysis revealed that virus-specific RNA was present only in the cytoplasm at both early and late times PI. When infected cell membranes were separated on a discontinuous sucrose gradient, most of the virus-specific RNA was associated with the endoplasmic reticulum fraction.
Exp Mol Pathol 1983 Apr
PMID:Japanese encephalitis virus replication: studies on host cell nuclear involvement. 640 79

Adenovirus early region 1A (E1A) is the first transcription unit expressed after infection. It encodes a protein which controls the expression of all other early viral genes. The E1A mRNAs have one major capped 5' terminus which maps 31 nucleotides downstream from a T-A-T-A sequence (C. Baker and E. Ziff. J. Mol. Biol. 149:189-221, 1981). In addition, a minor set of E1A mRNAs are observed during the early phase of infection which have 5' termini mapping at approximately -160, -185, and -230 relative to the major cap site (Osborne et al., Cell 29:139-148, 1982). Here we report the occurrence of another set of minor E1A mRNAs which were observed exclusively after the initiation of viral DNA replication. These late specific E1A mRNAs had cap sites which mapped at approximately -300, -325, -360, and -375 relative to the major cap site. The appearance of these minor late E1A mRNAs was blocked by the DNA synthesis inhibitor cytosine arabinoside. These same late specific E1A mRNAs were synthesized from E1A-containing plasmids which replicate in monkey cells. This demonstrated that neither late specific adenovirus proteins nor adenovirus-specific chromatin structure was required for the production of the late specific E1A mRNAs. Adenovirus mutants in which the E1A T-A-T-A box region had been deleted also synthesized the corresponding deleted forms of the late specific mRNAs after initiation of DNA replication. These results indicate that the process of DNA replication alters the specificity of E1A transcription initiation in a promoter region which is at least 375 nucleotides in length.
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PMID:Far upstream initiation sites for adenovirus early region 1A transcription are utilized after the onset of viral DNA replication. 683 69


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