Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear DNA helicase II (NDH II), alternatively named RNA helicase A (RHA), is an F-actin binding protein that is particularly enriched in the nucleolus of mouse cells. Here, we show that the nucleolar localization of NDH II of murine 3T3 cells depended on an ongoing rRNA synthesis. NDH II migrated out of the nucleolus after administration of 0.05 microg/ml actinomycin D, while nucleolin and the upstream binding factor (UBF) remained there. In S phase-arrested mouse cells, NDH II was frequently found at the nucleolar periphery, where it was accompanied by newly synthesized nucleolar RNA. Human NDH II was mainly distributed through the whole nucleoplasm and not enriched in the nucleoli. However, in the human breast carcinoma cell line MCF-7, NDH II was also found at the nucleolar periphery, together with the tumor suppressor protein p53. Both NDH II and p53 were apparently attached to the F-actin-based filamentous network that surrounded the nucleoli. Accordingly, this subnuclear structure was sensitive to F-actin depolymerizing agents. Depolymerization with gelsolin led to a striking accumulation of NDH II in the nucleoli of MCF-7 cells. This effect was abolished by RNase, which extensively released nucleolus-bound NDH II when added together with gelsolin. Taken together, these results support the idea that an actin-based filamentous network may anchor NDH II at the nucleolar periphery for pre-ribosomal RNA processing, ribosome assembly, and/or transport.
...
PMID:Nuclear DNA helicase II (RNA helicase A) binds to an F-actin containing shell that surrounds the nucleolus. 1472 62

Cell proliferation and apoptosis are controlled by tightly orchestrated signaling pathways that culminate in transcriptional activation/repression of multiple proteins. Dysregulation of cell cycle and/or apoptosis control may lead to genomic instability, neoplastic transformation and tumor progression. Under certain conditions, some hexavalent chromium [Cr(VI)] compounds are toxic and carcinogenic in the human respiratory tract, and we have shown that they induce apoptosis and/or cell cycle arrest in a p53-dependent fashion. There is increasing evidence linking extracellular signal-regulated kinase (ERK) activation with the DNA damage response, by both p53-dependent and -independent mechanisms. Here, the aim was to study the effect of Cr(VI) transcriptional regulation of key cell cycle inhibitors and pro- and anti-apoptotic proteins, as well as the role of ERK activation in the Cr(VI) genotoxic response. Diploid human lung fibroblasts were incubated with 3-9 uM Na2CrO4, and RNA was isolated at 4, 8, and 24 h, as well as 24 h after Cr(VI) exposure was terminated (recovery). mRNA expression was quantitated by RNase protection assay with a 32P-labeled multi-transcript probe containing gene sequences for the cdk inhibitors, p21waf1/cip1, p27kip1, p16INK4a, p15INK4b; the pro-apoptotic proteins bcl-XS and bax; the anti-apoptotic proteins bcl-W, bcl-XL, and bcl2, GADD45, and cyclin A. In general, bcl-W and bcl-XL expression were both downregulated after Cr exposure, to around 50% at 24 h, which was more pronounced after the recovery period. At Cr(VI) concentrations < or = 6 uM, bcl2 expression was upregulated. Of particular interest is that bax expression was reduced, in a dose and time-dependent fashion, however that of bcl-XS was elevated by nearly 3-fold after 8 h, and declined to control levels at the end of the recovery period. Expression of GADD45 and p21 were both upregulated by 2-fold at 8 h, but declined to control levels during recovery. Neither the expression of p27 nor that of p16 were apparently affected by Cr(VI) exposure, however the expression of p15 was markedly increased after exposure to all concentrations of Cr(VI). Finally, the expression of cyclin A was decreased after 24 h Cr(VI) exposure. Cr(VI) induced a transient burst of ERK activity (2-6-fold over control) around 0.5-3 h after exposure. However, inhibition of ERK activation with PD98059 had no effect on the Cr-induced alterations in gene expression. Moreover, Cr(VI)-induced clonogenic lethality, as assessed after 24 h exposure to 1 and 2 uM Cr(VI), was also not affected by ERK inhibition. These data suggest that both p53-dependent and -independent apoptotic and growth-inhibitory pathways are markedly affected by Cr(VI) exposure. However, the ability of Cr(VI) to affect key apoptotic and growth arresting genes, and thus clonogenic lethality, appears to be independent of ERK. Continued investigation into the cellular and molecular mechanisms of Cr(VI)-induced cell cycle and apoptosis control should further the understanding of Cr(VI)-associated carcinogenesis.
...
PMID:Induction of pro-apoptotic and cell cycle-inhibiting genes in chromium (VI)-treated human lung fibroblasts: lack of effect of ERK. 1497 55

Human hepatoma cell lines undergo apoptosis after treatment with cisplatin (CP), by mechanisms that are not fully understood, although our previous study demonstrated that Fas-dependent or -independent pathways are involved. To elucidate the mechanisms of CP-induced apoptosis in Hep3B cells, which are Fas- and p53-negative, we investigated mitochondria associated pathways, the involvement of NF-kappaB, and p73 activation. Results of Western blot and flow cytometry assay revealed that the translocation of Bax, resulted in the loss of mitochondrial membrane potential (Deltaphi(m)) and the efflux of cytochrome c and of second mitochondria-derived activator of caspase/DIABLO from mitochondria into the cytosol. Caspase-3, -8 and -9 were activated by CP treatment, however, CP-induced apoptosis was not completely blocked by pretreating with the pan-caspase inhibitor, benzyloxycarbonyl-valinyl-alaninyl-aspartyl-(O-methyl)-fluoromethylketone, indicating that caspase-independent apoptotic pathways might also be involved. RNase protection assay confirmed that NF-kappaB downregulation leading to the suppression of its target genes, such as XIAP and TRAF2, and p73 accumulation were also observed in Hep3B cells treated with CP. CP-induced apoptosis was inhibited to some extent by transiently overexpressed p73 dominant negative and XIAP, but not by p73DN or XIAP alone. In conclusion, this study demonstrates that CP-induced apoptosis in Hep3B cells is associated with mitochondrial dysregulation, NF-kappaB downregulation and p73 accumulation.
...
PMID:Cisplatin-induced apoptosis in Hep3B cells: mitochondria-dependent and -independent pathways. 1504 63

We have previously shown that mouse Dda3 gene is a p53 and p73 transcriptional target whose expression suppresses tumor cell growth. Here, we report the identification of multiple variants of Dda3 transcripts with diverse 5' sequences through 5'] rapid amplification of cDNA ends (5'-RACE) and RT-PCR. Analysis by primer extension and RNase protection revealed that the 5'-heterogeneity was generated by transcription initiation at multiple sites in exon 1 and intron 1 and by alternative splicing. These transcripts, both coding and non-coding, exhibited distinct expression patterns in various adult tissues and were developmentally regulated. Furthermore, they were induced in a p53-dependent manner by various stress signals. These data demonstrated that differential initiation of transcription and alternative splicing both participate in the regulation of Dda3 gene expression.
...
PMID:5'-Heterogeneity of mouse Dda3 transcripts is attributed to differential initiation of transcription and alternative splicing. 1511 Nov 31

Protein B23/nucleophosmin is a multifunctional protein that plays roles in ribosome biogenesis, control of centrosome duplication, and regulation of p53 expression. A yeast two-hybrid screen was performed in a search for interaction partners of B23. The complementary DNA for a highly acidic protein, nucleoplasmin 3 (NPM3), was found in multiple positive clones. Protein NPM3 and its interaction with B23 were further characterized. Endogenous B23 was able to be co-immunoprecipitated with NPM3, and this complex was resistant to ribonuclease treatment and high concentrations of salt. The N-terminal 35-90 amino acids of B23 were found to be required for their interaction. Separate co-immunoprecipitation studies of B23 and NPM3 suggested the existence of two different complexes, one containing B23 and 28 S ribosomal RNA (rRNA) and another composed of B23, NPM3, and other proteins, but no RNA. NPM3 was localized in the nucleolus, and its nucleolar localization depended on active rRNA transcription. In the cells overexpressing NPM3, there were decreased rates of pre-rRNA synthesis and processing. Overexpression of a mutant of NPM3 that did not interact with B23 did not alter pre-rRNA synthesis and processing, suggesting that the interaction of NPM3 with B23 plays a role in the ribosome biogenesis.
...
PMID:Protein NPM3 interacts with the multifunctional nucleolar protein B23/nucleophosmin and inhibits ribosome biogenesis. 1559 47

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.
...
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

Human monocytic THP-1 cells can be induced to differentiate to macrophages when treated with phorbol 12-myristate 13-acetate (PMA). It is understood that before initiating cell differentiation, PMA treatment must first induce an inhibition of cell growth. Since the initial biochemical and molecular events that are associated with this growth inhibition have not been characterized, the present study was carried out to elucidate the molecular mechanisms associated with the PMA-induced growth arrest of THP-1 cells. Our results indicate that PMA inhibits THP-1 cells at G1-phase of the cell cycle, via a complex mechanism associated with the modulation of the expression of several cell cycle regulators, initiated by the cellular generation of reactive oxygen species (ROS). Both p21WAF1/CIP1 mRNA and protein were upregulated 24 h post PMA treatment as demonstrated by ribonuclease protection assay and Western blotting, respectively. Because these cells lack functional p53, this effect was independent of p53 activity. Electrophoretic mobility shift assay showed that the PMA-induced activation of the p21WAF1/CIP1 promoter was driven by the specific protein 1 (Sp1) transcription factor through Sp1-binding sites. Additionally, our study demonstrates that PMA-induces the upregulation of p21 through a protein kinase C (PKC)-mediated ROS-dependent signaling mechanism involving MAP kinase activation.
...
PMID:Signal transduction of phorbol 12-myristate 13-acetate (PMA)-induced growth inhibition of human monocytic leukemia THP-1 cells is reactive oxygen dependent. 1597 37

We have previously shown p53 to have a specific role in osteoblast differentiation by its ability to regulate expression of certain bone specific proteins. In this study, we show mineralized matrix formation in vivo to be directly related to the presence of wild type p53 in osteoblastic osteosarcoma cells. In order to further understand the importance of p53 in differentiation, we investigated the relationship between p53 and Bone Morphogenetic Proteins (BMPs) (BMP 1, 2, 3A, 3B (GDF-10), 4, 5, 6, 7, 8A and 8B) during osteoblast differentiation. The expression of several BMPs were tested using RNase Protection Assay in differentiating ROS17/2.8 osteoblastic osteosarcoma cells. The expression of BMPs 1, 2, 3a, 3b and 7 showed time dependent modulation during in vitro differentiation. In order to determine if p53 has a role in this process, we used a murine osteosarcoma cell line stably expressing a temperature sensitive p53. Cells were exposed to ascorbic acid and glycerophosphates to hasten in vitro osteoblast differentiation and maintained either at 32 or 37 degrees C for expression of the wild type or mutant p53 phenotype. The expression of BMP-2, BMP-4 and BMP-7 were modulated in a p53 dependent fashion. We were able to confirm the p53 dependency of BMP-2 independently by RT-PCR. While BMP-2 expression was evident in the presence of both wild type and mutant p53, regulated expression was seen only in cells expressing wild type p53. Transient over expression of wild type p53 did not result in the same BMP-2 response as stable expression showing that the presence of p53 may be important for an orderly development of osteoblast differentiation rather than a direct effect on gene expression. The functional relationship between p53 and these bone specific markers is discussed.
...
PMID:Relationship of bone morphogenetic protein expression during osteoblast differentiation to wild type p53. 1599 55

Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased expression of neuronal nitric oxide synthase and increased 3-nitrotyrosine were observed in striatum of Nurr1 heterozygous (Nurr1 +/-) mice as compared with wild-type. Increased cytochrome C activation and consecutive release of Smac/DIABLO were also observed in Nurr1 +/- mice. An induction of active Caspase-3 and p53, cleavage of poly-ADP (RNase) polymerase and reduced expression of bcl-2 were observed in Nurr1 +/- mice. Methamphetamine significantly increased these markers in Nurr1 +/- mice as compared with wild-type. The present data therefore suggest that nitric oxide plays a role as a modulating factor for the increased susceptibility, but not the potentiation, of the dopaminergic terminals in Nurr1 +/- mice. We also report that this increased neuronal nitric oxide synthase expression and increased nitration in Nurr1 +/- mice led to the activation of apoptotic cascade via the differential alterations in the DNA binding activity of transcription factors responsible for the propagation of growth arrest as well as apoptosis.
...
PMID:Nitric oxide mediates increased susceptibility to dopaminergic damage in Nurr1 heterozygous mice. 1612 11

To clarify whether p53 mutation could be involved in the pathogenesis of various subtypes of lymphoma, we investigated 62 Japanese cases of non-Hodgkin's lymphomas (NHLs) for p53 gene mutations and their relationship with the expression of p53 protein. Mutations in exons 5-9 of the p53 gene were screened for using the non-isotopic RNase cleavage assay (NIRCA) and confirmed by direct sequencing, followed by immunohistochemical analysis for p53 protein. Missense and/or nonsense mutations of p53 were detected in 3 (10.7%) of 28 diffuse large B-cell lymphomas (DLBLs) and 2 (15.4%) of 13 T-cell NHLs (15.4%). A single missense mutation at codon 157 (Val to Phe) in exon 5 and at codon 273 (Arg to Pro) in exon 8 was found respectively in 2 DLBLs and in one peripheral T-cell lymphoma (unspecified). In these 3 cases harbouring a missense mutation, overexpression of p53 protein was observed in more than 80% of tumour cells. Double transversion mutations comprising of a missense mutation at codon 167 (Gln to His) in exon 5 and a nonsense mutation at codon 183 (Ser to stop codon) in exon 5 were detected in one DLBL that had apparently transformed from follicular lymphoma and in one advanced adult T-cell lymphoma (ATL). In these two cases harbouring p53 nonsense mutation, no cells positive for p53 protein immunostaining were detected, as well as lymphomas without p53 mutation.
...
PMID:Mutation of the p53 tumour suppressor gene and overexpression of its protein in 62 Japanese non-Hodgkin's lymphomas. 1760 75


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

---