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)

Cyclin and cyclin-dependent kinase(cdk) complexes, and their inhibitors (CKIs) play important roles in growth regulation on the cells. p27/kip1 is a CKI associated with G1 arrest induced by cell to cell contact, transforming growth factor-beta and cyclic AMP. The abnormality of p27/Kip1 genes in human tumors usually appears as a steady level defect of expression, since mutations in them is rare. Thus it is important to estimate the expression level of this gene. To detect the change of p27/Kip1 mRNA level in blood cells, we developed the ribonuclease protection assay using nonradioactive riboprobe which was produced by reverse transcriptase-polymerase chain reaction (RT-PCR) with T7 promoter-added antisense primer and the in vitro transcription system. Our assay may be useful for clinical evaluation of the mRNA level.
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PMID:[Detection of p27/kip1 mRNA in blood cells by nonradioactive ribonuclease protection assay]. 867 70

The cyclin-dependent kinase (CDK) inhibitor p18 blocks progression of the cell cycle by associating with the cyclin D-dependent kinases CDK6 and CDK4. To better understand the regulation of p18 gene expression, we isolated full-length cDNA clones from a human BT-20 breast cancer cell cDNA library. These clones were then used to isolate the human gene from a human genomic DNA library. The human p18 gene spans at least 7.5 kb and is composed of three exons, two of which encode the p18 protein. The genomic clone we isolated contained 5 kb of putative promotor sequence which directed expression of the luciferase reporter gene in transient transfection experiments. The longest cDNA that we isolated from BT-20 cells contained 2103 nucleotides which corresponds to the size of the major RNA transcript detected by Northern analysis in these cells. Transcription start sites mapping to the 5' end of the putative full-length cDNA were identified by ribonuclease protection assays. A novel polymorphism was identified in the 3' untranslated region of BT-20 cell cDNA clones that contained the previously described codon 72 mutation. The codon 72 mutation was also detected in 3 of 35 breast tumors analyzed using a mismatch PCR/RFLP strategy.
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PMID:Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer. 963 70

We have shown earlier that the cell growth inhibitory activity of interferon (IFN) is significantly enhanced by tunicamycin (TM) (Maheshwari et al., Science 219, 1339-1341, 1983). In this report, we investigated various regulatory points of synergistic action between TM and IFN-alpha/beta that inhibit cell growth in NIH 3T3 cells. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) viability assays showed a dose-dependent increase in percentage inhibition of the cells when treated with either TM or IFN. When doses of TM and IFN that had no significant inhibition on cell viability were used in combination, there was a pronounced suppression of DNA synthesis (tritiated thymidine incorporation). Flow cytometry studies revealed that individual treatments with either IFN or TM that did not alter the cell cycle profile, when combined, resulted in an impaired cell cycle by inhibiting G1/S progression. The blockage of G1/S transition was associated with reduction of cyclin-dependent kinase (CDK4) activity. The mRNA (analyzed by ribonuclease protection assay) and protein levels (assayed by Western blotting) of cyclins D1, D3, and CDK4 were downregulated by combined treatment with IFN and TM. An increase in the expression of p27/kipl, an inhibitor of CDK4, was observed in cells that were treated with both IFN and TM. These studies suggest that insufficient formation of the active cyclin/CDK complex could possibly be deferring the cells from normal cycling and may be responsible for the ability of TM to enhance cell growth inhibition induced by IFN.
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PMID:Tunicamycin enhances the anticellular activity of interferon by inhibiting G1/S phase progression in 3T3 cells. 1076 75

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of the cell population in G(2)/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znalpha(2)gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znalpha(2)gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162-169, 2001.
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PMID:Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression. 1145 81

In vitro expansion of chondrocytes for tissue-engineering applications is limited by forms of growth arrest known as quiescence and replicative senescence. At the molecular level cyclin-dependent kinase inhibitors (CDKIs) are involved in mediating growth arrest in the G1 phase of the cell cycle. Using ribonuclease protection assays and immunocytochemical staining methods, we quantitatively analyzed expression profiles of G1 cell cycle inhibitors at the mRNA and protein levels. These inhibitors included the CDKIs of the CIP/KIP family (p21CIP1 p27KIP1, and p57KIP2) and the INK4 family (p15INK4b, p16INK4a, p18INK4c, and p19INK4d) as well as the retinoblastoma protein-family (pRb, p107, and p130) and the tumor suppressor p53. Analysis was carried out in proliferating, quiescent, and senescent states of primary cultures of adult human nasoseptal chondrocytes. The most pronounced effect (p < 0.0001) between cultures in proliferation and cultures in growth arrest was an increased expression of the CDKIs p57KIP2 and p15INK4b for quiescent growth arrest, and of p16INK4a, p15INK4b, and p57KIP2 for senescent growth arrest. Thus, these cell cycle inhibitors represent potential candidates for selective intervention to promote cellular multiplication of chondrocytes undergoing in vitro expansion for tissue-engineering applications. Possible methods of modulation include the targeted elimination of specifically identified cell cycle inhibitors by antisense technologies.
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PMID:In vitro expansion of human nasoseptal chondrocytes reveals distinct expression profiles of G1 cell cycle inhibitors for replicative, quiescent, and senescent culture stages. 1573 62

Canonical growth factors act indirectly via receptor-mediated signal transduction pathways. Here, we report on an autonomous pathway in which a growth factor is internalized, has its localization regulated by phosphorylation, and ultimately uses intrinsic catalytic activity to effect epigenetic change. Angiogenin (ANG), a secreted vertebrate ribonuclease, is known to promote cell proliferation, leading to neovascularization as well as neuroprotection in mammals. Upon entering cells, ANG encounters the cytosolic ribonuclease inhibitor protein, which binds with femtomolar affinity. We find that protein kinase C and cyclin-dependent kinase phosphorylate ANG, enabling ANG to evade its inhibitor and enter the nucleus. After migrating to the nucleolus, ANG cleaves promoter-associated RNA, which prevents the recruitment of the nucleolar remodeling complex to the ribosomal DNA promoter. The ensuing derepression of rDNA transcription promotes cell proliferation. The biochemical basis for this unprecedented mechanism of signal transduction suggests new modalities for the treatment of cancers and neurological disorders.
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PMID:Molecular basis for the autonomous promotion of cell proliferation by angiogenin. 2791 33