Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone mRNA was isolated from mengovirus-infected Ehrlich ascites tumor cells at various times postinfection and quantitated in a reticulocyte cell-free protein-synthesizing system. The amount of translatable histone mRNA decreases during the first hour postinfection by 30%, rises during the following 1-1.5 h by 10-15%, drops progressively in the further course of infection, and reaches 20% of the control at the end of the infectious cycle (8-9 h postinfection). On the basis of the relative histone mRNA contents, the histone-synthesizing potentials of mengovirus-infected Ehrlich ascites tumor cells are substantially higher throughout infection than actually expressed in vivo. This result indicates that the virus-induced shutoff of histone synthesis is not directly the consequence of inactivation or degradation of histone mRNA. Most of the histone mRNA recovered from mengovirus-infected Ehrlich ascites tumor cells is bound to ribosomes. Late in infection, certain mRNAs are co-isolated with histone mRNAs, very likely due to loss or shortening of poly(A) occurring after release of the mRNAs from polyribosomes.
 ...
PMID:Fate of histone messenger RNA in mengovirus-infected Ehrlich ascites tumor cells. 20 58

Under normal conditions, mammalian cells will not initiate mitosis in the presence of either unreplicated or damaged DNA. We report here that staurosporine, a tumor promoter and potent protein kinase inhibitor, can uncouple mitosis from the completion of DNA replication and override DNA damage-induced G2 delay. Syrian hamster (BHK) fibroblasts that were arrested in S phase underwent premature mitosis at concentrations as low as 1 ng/ml, with maximum activity seen at 50 ng/ml. Histone H1 kinase activity was increased to approximately one-half the level found in normal mitotic cells. Inhibition of protein synthesis during staurosporine treatment blocked premature mitosis and suppressed the increase in histone H1 kinase activity. In asynchronously growing cells, staurosporine transiently increased the mitotic index and histone H1 kinase activity but did not induce S phase cells to undergo premature mitosis, indicating a requirement for S phase arrest. Staurosporine also bypassed the cell cycle checkpoint that prevents the onset of mitosis in the presence of damaged DNA. The delay in mitotic onset resulting from gamma radiation was reduced when irradiation was followed immediately by exposure to 50 ng/ml of staurosporine. These findings indicate that inhibition of protein phosphorylation by staurosporine can override two important checkpoints for the initiation of mitosis in BHK cells.
 ...
PMID:Staurosporine overrides checkpoints for mitotic onset in BHK cells. 146 8

Histone deacetylases of Ehrlich ascites tumor cells are active at low temperatures (0-4 degrees C). The so-called hyperacetylated state of histones is the physiological state of histones in intact Ehrlich ascites tumor cells which is conserved by the continuous presence of 10 mM sodium butyrate during the preparation of nuclei and histones. Isolation of histones in the absence of butyrate causes an artificial decrease in histone acetylation. This artificial loss of histone acetylation produces a decrease of the elongation reaction in the RNA synthesis. The initiation of RNA synthesis is not affected.
 ...
PMID:Conservation of the acetylation pattern of histones and the transcriptional activity in Ehrlich ascites tumor cells by sodium butyrate. 618 52

Histone acetylation in transcriptionally inactive chromatin has been studied with chromatin containing mouse satellite DNA. The latter was obtained by digestion of nuclei from Ehrlich ascites tumor cells with the restriction nuclease Bsp, which degrades main-band DNA but leaves satellite DNA intact. The enzyme-resistant material was separated by gel filtration. Satellite DNA amounted to 65% of the total DNA in this fraction. When the cells were grown in the presence of sodium n-butyrate to inhibit histone deacetylation, a few, if any, hyperacetylated forms of core histones were found in satellite chromatin. Conversely, the highest quantity of tetraacetylated H4 molecules was found in the fractions containing the most extensively degraded chromatin.
 ...
PMID:Histone acetylation in chromatin containing mouse satellite DNA. 685 48

Activity of chromatin-bound protease of rat liver and Morris hepatoma 7777 was studied. Proteolytic enzyme was copurified with histones during extraction of chromatin with 0.25 M HCl. Total histone was fractionated by Oliver's et al. method. Histone fractions were incubated in 0.01 M Tris-HCl buffer (pH 7.6) at 37 degrees C within different periods of time. The behavior of these fractions in polyacrylamide gel electrophoresis as well as the amounts of peptides soluble in 5% TCA released during incubation indicated that enzyme was coextracted with histone H2B only. It was shown that the activity of protease coextracted selectively with histone H2B was higher in tumor tissue than in normal liver.
 ...
PMID:Activity of chromatin-bound protease in histone fractions from rat liver and Morris hepatoma. 700

A protein kinase that phosphorylates a specific KSP sequence [K(S/T)PXK], which is abundant in high molecular weight neurofilament (NF) proteins, was identified and isolated from rat spinal cord. Characterization of this enzyme activity revealed a close relationship with p34cdc2 kinase with respect to its molecular mass (32.5 kDa by SDS/PAGE) and substrate specificities. It could phosphorylate a synthetic peptide analog of the simian virus 40 large tumor antigen, reportedly a specific substrate for p34cdc2 kinase. Histone (H1) and peptide analogs of the KSP sequence present in the C-terminal end of rat and mouse neurofilament proteins were phosphorylated. This kinase did not phosphorylate alpha-casein and peptide substrates of other known second messenger-dependent or -independent kinases. Dephosphorylated rat NF protein NF-H was strongly phosphorylated by the purified enzyme; NF proteins NF-M and native NF-H, but not NF-L, were slightly phosphorylated. Studies on synthetic peptide analogs of KSP repeats with substitution of specific residues, known to be present in the C-terminal regions of NF-H, revealed a consensus sequence of X(S/T)PXK, characteristic of the p34cdc2 kinase substrate. On Western blots, the enzyme was immunoreactive with antibody against the C-terminal end of cdc2 kinase (mouse) and neuronal cdc2-like kinase from rat but not with an antibody against the conserved PSTAIRE region of the p34cdc2 kinase. The antibody against the C-terminal end of cdc2 kinase could immunoprecipitate (immunodeplete) the purified kinase activity. Since the adult nervous system is composed primarily of postmitotic cells, the present observations indicate a nonmitotic role for this cdc2-like kinase activity. The effective phosphorylation of NF-H by this kinase suggests a function in axonal structure.
 ...
PMID:cdc2-like kinase from rat spinal cord specifically phosphorylates KSPXK motifs in neurofilament proteins: isolation and characterization. 834 7

Histone genes display a peak in transcription in early S phase and are ideal models for cell cycle-regulated gene expression. We have previously shown that the transcription factor interferon regulatory factor 2 (IRF-2) can activate histone H4 gene expression. In this report we establish that a mouse histone H4 gene and its human homolog lose stringent cell cycle control in synchronized embryonic fibroblasts in which IRF-2 has been ablated. We also show that there are reduced mRNA levels of this endogenous mouse histone H4 gene in the IRF-2(-/-) cells. Strikingly, the overall mRNA level and cell cycle regulation of histone H4 transcription are restored when IRF-2 is reintroduced to these cells. IRF-2 is a negative regulator of the interferon response and has oncogenic potential, but little is known of the mechanism of these activities. Our results suggest that IRF-2 is an active player in E2F-independent cell cycle-regulated gene expression at the G1/S phase transition. IRF-2 was previously considered a passive antagonist to the tumor suppressor IRF-1 but can now join other oncogenic factors such as c-Myb and E2F1 that are predicted to mediate their transforming capabilities by actively regulating genes necessary for cell cycle progression.
 ...
PMID:Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2. 941 64

Histone acetylation levels in cells result from a dynamic equilibrium between competing histone acetylases and deacetylases. Changes in histone acetylation levels occur during both transcriptional activation and silencing. Cloning of the cDNA for a human histone deacetylase (HDAC1) has shown that it represents a human ortholog of the yeast transcriptional regulator RPD3. We have screened the expressed sequence tag database (National Center for Biotechnology Information) with the yeast RPD3 sequence and identified a human ortholog of RPD3, HDAC3. This cDNA encodes a protein of 428 amino acids with 58% sequence identity with HDAC1p. By using a specific polyclonal antiserum recognizing the C-terminal domain of HDAC3p and Western blotting, we detected a single approximately 49-kDa band in several tumor cell lines. HDAC3p is expressed predominantly in the nuclear compartment. Immunoprecipitation experiments with either an antiserum against HDAC3p or an anti-FLAG antiserum and a flagged HDAC3 cDNA showed that HDAc3p exhibits deacetylase activity both on free histones and on purified nucleosomes. This deacetylase activity is inhibited by trichostatin, trapoxin, and butyrate in vitro to the same degree as the deacetylase activity associated to HDAC1p. These observations identify another member of a growing family of human HDAC genes.
 ...
PMID:Characterization of a human RPD3 ortholog, HDAC3. 950 Nov 69

Patients carrying mutations in BRCA1 or BRCA2 tumor suppressor genes have shown to have high risk in developing breast and ovarian cancers. Two potential functions of BRCA2 were proposed which includes role in the regulation of transcription and also in DNA repair. Forty-five-amino acid region encoded by exon 3 of BRCA2 was shown to have transcriptional activation function. Recent studies of the several enzymes involved in acetylation and deacetylation of histone residues have revealed a possible relationship between gene transcriptional activation and histone acetylation. Since BRCA2 appear to function as a transcriptional factor, we have tested for Histone acetyl transferase (HAT) activity of BRCA2. Here, we present evidence that BRCA2 has intrinsic HAT activity, which maps to the amino-terminal region of BRCA2. Our results demonstrate that BRCA2 proteins acetylate primarily H3 and H4 of free histones. These observations suggest that HAT activity of BRCA2 may play an important role in the regulation of transcription and tumor suppressor function.
 ...
PMID:The BRCA2 is a histone acetyltransferase. 961 37

The ribonucleoprotein complex telomerase, which was found to be active in germ line, immortal, and tumor cells, and in cells from continuously renewing normal tissues such as epidermis or bone marrow, is thought to be correlated with an indefinite life span. Therefore, it has been postulated that in the normal tissues, telomerase activity may be restricted to stem cells, the possible precursors of tumor cells. Here, we demonstrate that a 56% enriched population of epidermal stem cells exhibited less telomerase activity than the more actively proliferating transit amplifying cells, which are destined to differentiate after a finite number of cell divisions. Thus telomerase is not a stem cell marker. In human epidermis we found a heterogeneous expression of the telomerase RNA component (hTR) within the basal layer, with clusters of hTR-positive cells showing variable activities. Histone-3 expressing S-phase basal cells were distributed evenly, illustrating that hTR upregulation may not strictly be correlated with proliferation. We further show for human epidermal cells that differentiation-dependent downregulation of telomerase correlates with Ca++-induced cell differentiation and that increasing the amount of Ca++ but not Mg++ or Zn++ reduced telomerase activity in a dose-dependent manner in a cell-free system (differentiation-independent). Furthermore, addition of ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid completely reversed this Ca++-induced inhibition. These data indicate that Ca++ is not only an important regulator of epidermal differentiation but also a key regulator of telomerase.
 ...
PMID:Telomerase is not an epidermal stem cell marker and is downregulated by calcium. 985 15


1 2 3 4 5 6 7 8 9 10 Next >>