Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrocyte apoptosis signaled through the Fas receptor has been proposed as a mechanism for the cytotoxicity observed in thyroiditis, but the role the Fas pathway plays in thyroid cancer is not known. We examined Fas expression in thyroid tissue derived from patients with papillary carcinoma and follicular cancer. More intense immunohistological staining for the Fas protein was observed on papillary cancer cells as compared with adjacent normal follicles. To further characterize the expression of Fas in papillary cancer, paired normal and cancerous thyroid tissues were obtained at thyroidectomy from several donors, digested, and placed into cell culture. Messenger RNA was analyzed by ribonuclease protection assays, and protein was identified by flow cytometry. Fas expression was detected at levels up to 3-fold higher in cancerous thyrocytes compared with paired normal cells. To determine whether the expressed Fas antigen was functional, thyrocytes were treated with a monoclonal IgM anti-Fas antibody (clone CH11; Upstate Biotechnology, Inc., Lake Placid, NY) in the presence of interferon-gamma and cycloheximide. Whereas both normal and cancerous thyrocytes were induced to die after this treatment, the cancerous thyrocytes were more sensitive to anti-Fas antibody. This work demonstrates that the Fas antigen is expressed and functional on papillary thyroid cancer cells and this may have potential therapeutic significance.
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PMID:Fas (CD95) expression is up-regulated on papillary thyroid carcinoma. 1056 80

Virus-infection of mammalian cells causes transcriptional induction of many cellular genes, collectively called as "viral stress-inducible genes." The proteins encoded by these genes are essential to maintain cell-virus homeostasis, which is required for both virus replication and host survival. Many viral products, including RNA, DNA, and proteins, can induce these genes by using distinct, but partially overlapping, signaling pathways. Type I interferons, direct products of virus infection, can also induce many of these genes, thus providing a positive feedback loop. Double-stranded RNA, a common by-product of virus replication, can induce them by multiple signaling pathways initiated by Toll-like receptor 3 or RIG-I/Mda-5. Several viral stress-inducible proteins inhibit protein synthesis. Proteins of the P56 family bind to the translation initiation factor, eIF-3, and block translation initiation. PKR, a protein kinase, phosphorylates a different initiation factor, eIF-2, and inhibits translation initiation. However, unlike P56, PKR needs to be first activated by dsRNA or PACT, another cellular protein. Another family of enzymes, the 2'-5' oligoadenylate synthetases, synthesizes 2'-5' linked oligoadenylates [2-5(A)] in the presence of dsRNA; 2-5(A) activates the latent ribonuclease, RNase L, which degrades mRNA. Many viruses have evolved mechanisms to evade these genes by blocking their induction or actions; often more than one strategy is used by the same virus to achieve this goal. Thus, in an infected cell, equilibrium is reached between the virus and the cell with regards to the viral stress-inducible genes.
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PMID:Viral stress-inducible genes. 1776 7

The human ribonuclease Dicer and its double-stranded RNA (dsRNA)-binding protein (dsRBP) partners TRBP and PACT play important roles in the biogenesis of regulatory RNAs. Following dicing, one dsRNA product strand is preferentially assembled into an RNA-induced silencing complex (RISC). The mechanism of strand selection in humans and the possible role of Dicer in this process remain unclear. Here we demonstrate that dsRNAs undergo significant repositioning within Dicer complexes following dicing. This repositioning enables directional binding of RNA duplexes, thereby biasing their orientation for guide strand selection according to the thermodynamic properties of the helix. Our findings indicate that Dicer is itself capable of sensing siRNA thermodynamic asymmetry regardless of the dsRBP to which it is bound. These results support a model in which Dicer employs two distinct RNA-binding sites-one for dsRNA processing and the other for sensing of siRNA thermodynamic asymmetry-during RISC loading in humans.
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PMID:siRNA repositioning for guide strand selection by human Dicer complexes. 2172 14

One of the cellular functions of the ribonuclease Dicer is to process microRNA precursors (pre-miRNAs) into mature microRNAs (miRNAs). Human Dicer performs this function in cooperation with its protein partners, AGO2, PACT and TRBP. The exact role of these accessory proteins in Dicer activity is still poorly understood. In this study, we used the northern blotting technique to investigate pre-miRNA cleavage efficiency and specificity after depletion of AGO2, PACT and TRBP by RNAi. The results showed that the inhibition of either Dicer protein partner substantially affected not only miRNA levels but also pre-miRNA levels, and it had a rather minor effect on the specificity of Dicer cleavage. The analysis of the Dicer cleavage products generated in vitro revealed the presence of a cleavage intermediate when pre-miRNA was processed by recombinant Dicer alone. This intermediate was not observed during pre-miRNA cleavage by endogenous Dicer. We demonstrate that AGO2, PACT and TRBP were required for the efficient functioning of Dicer in cells, and we suggest that one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of Dicer.
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PMID:The role of Dicer protein partners in the processing of microRNA precursors. 2216 34