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)

Ferritin synthesis is regulated at the translational level by iron, but it is likely that transcriptional regulation of H and L genes is responsible for tissue-specific distribution of H and L mRNAs. In order to define the regions important for transcriptional regulation of the mouse ferritin H gene, we have linked the promoter, including the transcription start site, and 5 kilobases of upstream sequence to a reporter gene (human growth hormone). This construct and a series of 5' deletion mutants have been used to transfect erythroid (K562, mouse erythroleukemia (MEL)) and hepatoma (HepG2) cell lines. Measurement of growth hormone in the culture medium and analysis of ferritin-growth hormone transcripts by a ribonuclease protection assay revealed that a 140-base pair minimal promoter is sufficient to confer a high level of expression to the reporter gene in both cell types. In addition, a 180-base pair fragment, lying 4.5 kilobases upstream of the ferritin transcription start site, functions like an inducible enhancer during N,N'-hexamethylene-bis-acetamide-induced differentiation of MEL cells. A perfect match to a consensus binding motif to the erythroid transcription factor NF-E2 is present in this regulatory element, but the mutant NF-E2 enhancer retains the inducible activity in stably transfected MEL cells, and the results from gel retardation assays suggest that protein-DNA complexes that form in vitro between the ferritin enhancer and MEL nuclear extracts do not contain NF-E2. Thus, nuclear factors that mediate inducibility of the ferritin enhancer remain to be identified.
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PMID:Mouse ferritin H subunit gene. Functional analysis of the promoter and identification of an upstream regulatory element active in erythroid cells. 805 Nov 21

Oxidative stress due to generation of reactive oxygen species (ROS) can cause damage to cellular proteins, lipids and DNA, which is one of crucial causes responsible for cancer. Nuclear factor erythroid 2 [NF-E2]-related factor 2 (NRF2) is a transcription factor of a variety of antioxidant and cytoprotective enzymes, so that it reduces the levels of damaging ROS in the cell. Over expression of NRF2 in cancer cells can enhance cancer progression, confer resistance to chemo and radiotherapy, and metastasis through the process of epithelial-to mesenchymal transition (EMT); which is a hallmark of cancer-related death. Dicer, a key component of the microRNAs biogenesis, is a ribonuclease enzyme which involves in maturation of microRNAs that have a role in distinct steps of metastasis cascade. Moreover, Dicer was found to be regulated by ROS/NRF2 interaction to contribute to activation of DNA damage repair mechanism. In addition, Dicer is directly reduced by mir-103/107 family that confers migratory capacity through down-regulation of mir-200 family (mir-200b/mir-200c/mir-429). Mir-200c and mir-34a were predicted to target the repressor of NRF2; Sirt1. On the other hand, mir-200a and mir-141 (mir-200 family) were detected to regulate NRF2 expression. This review highlights the regulation of redox homeostasis that is mediated by NRF2 could be modulated by metastasis regulating microRNAs under the control of Dicer. In addition, NRF2 may indirectly control DNA damage repair and microRNAs processing machinery through the crosstalk between NRF2 and Dicer. Understanding such interrelations could provide and shed light on the significance of microRNA-based therapies that will improve the action of clinically used cancer treatments.
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PMID:Crosstalk between NRF2 and Dicer through metastasis regulating MicroRNAs; mir-34a, mir-200 family and mir-103/107 family. 3214 89