Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the following 3 points: 1) tumor proliferation is energy-dependent, 2) mitochondrial energy-production system is dominant for cell growth, and 3) liver mitochondria (mt) possess their own DNA and RNA synthesizing some of their own proteins including respiratory enzymes such as cytochrome oxidases, a possible relationship between mutations of mt-DNA and clinical status of cell proliferation was examined in 10 HCC patients who underwent liver resection. Mt-DNA at the cancerous and the noncancerous portions of 1g resected liver specimens were separated from the nuclear DNA, and then digested with Hinf I endonuclease. DNA filters were made of the digested mt-DNA fragments on the agarose and polyacrylamide gel. The filters were hybridized with a nick-translated 32P-labeled DNA fragments. In two cases, abnormal mt-DNA were detected. In the first case, the tumor was the massive type and grew rapidly invading the bile duct. One restriction fragment of 3.0 Kb of the cancerous and non cancerous portion became larger by 60 bp. In the second case, regarded as metachronous multicentric HCC, the second largest band of the 3.4 Kb fragment of the cancerous portion showed a wider range but not of the noncancerous portion. The former change may indicate polymorphism but the latter indicates an occurrence of the mutation of mt-DNA. Further studies are required, including examinations on the rest of mitochondrial fragments.
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PMID:[Analysis of human mitochondrial DNA in hepatocellular carcinomas]. 283 32

The binding of aflatoxin B1, AFB1, a potent hepatocarcinogen, to various high molecular weight (HMW) DNAs from human normal liver and two liver cancer cell lines, Alexander primary liver carcinoma (PLC) and Mahlavu hepatocellular carcinoma (hHC) and from NIH/3T3 cell have been investigated. The kinetics of AFB1 binding to these DNAs showed similar initial rates but the extents of binding to the PLC and hHC DNAs seemed to be slightly higher. Preferential AFB1 bindings were identified in both PLC and hHC DNAs compared to normal liver DNA when analyzed by restriction endonuclease digestions and agarose gel electrophoresis. A critical AFB1 binding dosage, ranging 100 to 460 fmole/microgram DNA, was found to activate the carcinogenic effect of the Mahlavu hHC HMW DNA, but not normal liver HMW DNA, rendering it capable of inducing focal transformation in NIH/3T3 cell. Excessive AFB1 binding on the hHC and PLC HMW DNAs resulted in an "over-kill" of both cell transformation capability and templating activity of the DNA.
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PMID:Dose dependency of aflatoxin B1 binding on human high molecular weight DNA in the activation of proto-oncogene. 300 75

The cytotoxicity of gamma-hexachlorcyclohexane (gamma-HCC) was evaluated in HL-60 cells. Gamma-HCC dose-dependently induced cytotoxicity of HL-60 with an IC50 value of 60+/-5 microM. The gamma-HCC treated cells showed some characteristic changes of apoptosis, including blebbing of the membrane, condensation of the nuclear chromatin, vacuolation of cytoplasm and internucleosomal DNA fragmentation. Gamma-HCC induced DNA fragmentation of HL-60 cells in a dose-, time- and Ca2+-dependent manner. The DNA fragmentation induced was inhibited by intracellular Ca2+ chelator, calmodulin antagonist and Ca2+ sensitive endonuclease inhibitor. Gamma-HCC caused a steady increase in the cytosolic free Ca+ concentration due to release from intracellular stores. Neither the DNA fragmentation nor the increase of intracellular Ca2+ induced by gamma-HCC was inhibited by the removal of extracellular Ca2+. These data suggested that the cytotoxicity of gamma-HCC in HL-60 cells is mediated by the increase of intracellular Ca2+ concentration and the activation of Ca2+-dependent endonuclease, which triggers apoptosis in a Ca2+ and calmodulin-dependent manner.
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PMID:Mediation of gamma-hexachlorocyclohexane-induced DNA fragmentation in HL-60 cells through intracellular Ca2+ release pathway. 967 59

Long interspersed nucleotide element (LINE-1; L1) as an autonomous retrotransposon is localized usually in AT-rich, low-recombined, and gene-poor regions of genome. It is transiently activated in embryonic development and continuously activated in all tumor cells tested so far. Full-length L1 gene contains 5' untranslated region, two open reading frames (ORFs) encoded L1ORF1p and L1ORF2p, and a 3' terminal polyadenylation site. Compared with L1ORF2p, a protein encompassing reverse transcriptase and endonuclease activities, L1ORF1p remains to be elucidated. With liver cancer cells and tissues, the expression and sub-localization of L1ORF1p were investigated and shown that L1-ORF1p expresses just in liver cancer cells and tissues but not in normal liver cells and almost not in adjacent tissues. To characterize L1ORF1p, the strategies for over-expression and down-regulation of L1ORF1p in transfected cells were implemented. The phenomenon of promoting cell proliferation and colony formation was observed in transfected cells with L1ORF1p over-expression and vice versa. Down-regulation of L1ORF1p suppresses tumorigenesis in vitro and in vivo. Smad4 as an interaction protein of L1ORF1p is identified for the first time, while L1ORF1p is responsible for Smad4 sequestration in the cytoplasm. Thus, L1ORF1p contributed to tumorigenesis and may attribute to, at least partly, its participation in Smad4-signaling regulation.
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PMID:L1-ORF1p, a Smad4 interaction protein, promotes proliferation of HepG2 cells and tumorigenesis in mice. 2386 96

Exonuclease 1 (EXO1), a member of the RAD2 nuclease family, was first described as possessing 5' to 3' nuclease activity and 5' structure-specific endonuclease activity. Here, we show that EXO1 is significantly upregulated in HCC tumor tissues and that high EXO1 expression is significantly correlated with liver cirrhosis. We further demonstrate that EXO1 knockdown decreases proliferation and colony forming abilities of HCC cells in vitro and tumorigenicity in vivo, as well as decreases migration and invasive capabilities of HCC cells. Alternatively, EXO1 overexpression significantly increases the proliferation, colony forming ability, and migration and invasive capabilities of HCC cells in vitro. Additionally, we truncated a region upstream of the transcription start site (TSS) of EXO1 and used the region with the strongest transcriptional activity to predict that the transcription factor FOXP3 can bind to the EXO1 promoter. Bioinformatics analysis found that FOXP3 was positively correlated with EXO1 and luciferase reporter assays and RT-PCR confirmed that FOXP3 could enhance the transcriptional activity of EXO1. CCK-8 assays showed that depletion of FOXP3 further reduces cell proliferation ability after knocking down of EXO1 in vitro. Taken together, our findings indicate that EXO1 acts as an oncogene in HCC and its expression level is related to FOXP3 activity.
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PMID:EXO1 Plays a Carcinogenic Role in Hepatocellular Carcinoma and is related to the regulation of FOXP3. 3262 39