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

Adenovirus type 4 (Ad4) is the sole member of adenovirus group E based on overall DNA sequence homology, restriction endonuclease cleavage patterns, and the size of capsid proteins. We cloned the BamHI-F fragment from the left end of Ad4 in pUC13-1 between the SalI and BamHI sites in order to carry out the structural analysis of the E1A region of Ad4. The complete sequence of the BamHI-F fragment (2042 bp) has been determined. From the DNA sequence, the splice sites for the putative 12 S and 13 S mRNAs, encoded by the E1A region of Ad4 were deduced. If protein synthesis initiates at the first available AUG triplet (position 575), these 12 S and 13 S mRNAs would code for polypeptides containing 226 and 257 amino acids, respectively. Comparison of Ad4- and Ad7-13 S mRNA-coded polypeptides indicates that there is 57% homology, whereas the homology is only 38% with Ad12 and 31% with Ad2-13 S mRNA-coded polypeptides. The structural analysis in the E1 region of Ad4 also includes the coding region for the E1B 19-kDa protein. Ad4 and Ad7 shows 65% homology in the coding regions for E1B 19-kDa protein. Comparison of the DNA sequence of Ad4 with those of Ad2, Ad7, and Ad12 by using a dot matrix computer program and by Southern hybridization revealed that Ad4 bears a stronger homology with Ad7 than with Ad2 and Ad12 in this region. Hydropathy plots and alignments of the putative polypeptides coded by this region in Ad4 with those from the corresponding regions of different serotypes to reveal the highly conserved domains also support the above conclusion.
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PMID:Sequence analysis in the E1 region of adenovirus type 4 DNA. 294 81

An adenovirus (Ad) interserotypic recombinant (H2cyt141) between temperature-sensitive mutant H2ts111 of Ad2 and deletion mutant H5dl313 of Ad5 was isolated and characterized. It was phenotypically ts+, dl+, hr+ and formed large plaques (or cytocidal: cyt). It contained the right 89% of Ad5 DNA and the leftmost 11% of Ad2 DNA. Genetic recombination data suggested the cytocidal mutation lay in the transforming region E1B, confirming sequence analysis. The cytocidal effect resulted in part from the breakdown of cellular DNA. Host cell and virus DNA breakdown induced by H2cyt141 appeared cell-dependent: it occurred in HeLa, KB or BHK-21 cells, but not in CV1 or 293 cells. In human cells the cyt effect was recessive and adenovirus DNA degradation was prevented by co-infection with adenovirus wild-type (H2WT), other adenovirus serotypes or simian virus 40 (SV40). In simian cells, H2cyt141 did not inhibit SV40 DNA replication, unlike H2WT. The amount of H2cyt141 DNA integrated in human cell DNA at early stages of the lytic cycle was found to be significantly lower than for H2WT. Novobiocin inhibited viral DNA breakdown in human cells. Cellular DNA extracted from H2cyt141-infected cells exhibited a repeat band pattern in gel electrophoresis reminiscent of the nuclease digestion pattern of chromatin, with monosome-size fragments as the digestion limit. The H2cyt141-induced nucleolytic effect would therefore occur in the linker regions of cell DNA and might result from the observed stimulation (by a factor of greater than 100) of an acidic (optimum pH 4.0) endonuclease activity. The nucleolytic effect also appeared to be recessive in vitro and absent in mixed samples containing extracts from H2cyt141-infected cells plus extracts from H2WT- or mock-infected cells. The virus gene product responsible for the enhancement of the acidic endonuclease was found to function stoichiometrically and not catalytically. The cytocidal and nucleolytic effects of the viral E1B region 19K protein may be mediated by a cellular inhibitor of acidic endonuclease.
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PMID:An adenovirus cytocidal function related to the control of a cellular pH 4 endonuclease activity. 299 79

A total of 59 cytocidal (cyt) mutants were isolated from adenovirus 2 (Ad2) and Ad5. In contrast to the small plaques and adenovirus type of cytopathic effects produced by wild-type cyt+ viruses, the cyt mutants produced large plaques, and the cytopathic effect was characterized by marked cellular destruction. cyt mutants were transformation defective in established rat 3Y1 cells. cyt+ revertants and cyt+ intragenic recombinants recovered fully the transforming ability of wild-type viruses. Thus, the cyt gene is an oncogene responsible for the transforming function of Ad2 and Ad5. Genetic mapping in which we used three Ad5 deletion mutants (dl312, dl313, and dl314) as reference deletions located the cyt gene between the 3' ends of the dl314 deletion (nucleotide 1,679) and the dl313 deletion (nucleotide 3,625) in region E1B. Restriction endonuclease mapping of these recombinants suggested that the cyt gene encodes the region E1B 19,000-molecular-weight (175R) polypeptide (nucleotides 1,711 to 2,236). This was confirmed by DNA sequencing of eight different cyt mutants. One of these mutants has a single missense mutant, two mutants have double missense mutations, and five mutants have nonsense mutations. Except for one mutant, these point mutations are not located in any other known region E1B gene. We conclude that the cyt gene codes for the E1B 19,000-molecular-weight (175R) polypeptide, that this polypeptide is required for morphological transformation of rat 3Y1 cells, and that simple amino acid substitutions in the protein can be sufficient to produce the cyt phenotype.
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PMID:cyt gene of adenoviruses 2 and 5 is an oncogene for transforming function in early region E1B and encodes the E1B 19,000-molecular-weight polypeptide. 649 62

We have analysed early viral gene products expressed in adenovirus type 12 (Ad12)-infected cells as well as in two Ad12-transformed hamster cell lines, and Ad12-induced rat tumour cell lines by cell-free translation of virus-specific RNA which was selected by hybridization to cloned restriction endonuclease fragments of virus DNA. Proteins synthesized in vitro were analysed by one- and two-dimensional gel electrophoresis. It was found that RNA encoded by early region E1A directs the synthesis of at least eight polypeptides with apparent mol. wt. 38K, 36K, 30K, 28K, 26K, 25K, 24K and 22K. All these proteins are related to each other. E1B-specific RNA directs the synthesis of three proteins: 59K, 19K and 17K. Early region E2a codes for a 61K polypeptide which probably represents the single-strand DNA-binding protein of Ad12. RNA complementary to region E3 directs the synthesis of a 16K protein, and RNA transcribed from region E4 the synthesis of polypeptides with mol. wt. 20K, 18K and 11.5K. We have mapped a 67K polypeptide into the region within 11 to 28 map units (E2b). The analysis of proteins directed by virus-specific RNAs prepared from two Ad12-transformed hamster cell lines (T637, HA12/7) and one Ad12-induced rat tumour line (RBT12/3) showed that early regions E1 and E4 are expressed in all three Ad12-transformed cell lines. RNA transcribed from early regions E2 and E3 have been detected in lines T637 and RBT12/3. The virus RNA prepared from the Ad12-transformed cell lines directed synthesis of polypeptides with mol. wt. very similar to those of early virus proteins from infected cells. However, in all three Ad12-transformed cell lines mentioned above we have found RNAs which directed the synthesis of additional polypeptides of early regions E1 (34K) and E4 (25K, 24K) not detected in infected cells. The DNA sequence between 11 and 28 map units (coding for the 67K protein) is not expressed in the Ad12-transformed cells.
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PMID:Expression of early viral gene products in adenovirus type 12-infected and -transformed cells. 709 53

B lymphocytes from patients with systemic lupus erythematosus (SLE) are characterized by reduced expression levels of membrane CD5. Recent studies from our laboratory have revealed that the level of membrane CD5 is determined by the relative level of two alternative CD5 isoforms; CD5-E1A, which is expressed on the membrane, and CD5-E1B, which is retained in the cytoplasm. Using bisulfite sequencing and methylation-sensitive endonuclease assays we show that the promoter for the alternative CD5-E1B isoform is demethylated in B cells from patients with SLE but not in healthy controls. We go on to show that differential methylation is more pronounced following BCR engagement. As a result of this demethylation, CD5-E1B mRNA is transcribed at the expense of CD5-E1A mRNA transcription. We provide further evidence that production of high IL-6 levels by SLE B cells abrogates the ability of SLE B cells to induce DNA methyl transferase (DNMT1) and then to methylate DNA, an effect that is reversed in the presence of a blocking Ab to the IL-6 receptor. The pattern of demethylation of CpG islands in the CD5-E1B promoter in SLE B cells is similar to those in B cells from healthy controls stimulated in the presence of IL-6, or treated with the methylation inhibitor PD98059. The study reveals that engagement of the BCR with constitutive IL-6 down-regulates the level of membrane CD5, which negatively regulates BCR signaling, in SLE B cells. This altered signaling could, in turn, promote the activation and expansion of autoreactive B cells in SLE patients.
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PMID:IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. 1938 Aug 9