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)

Moloney murine leukemia virus (MuLV) can be a potent inducer of promonocytic leukemias in mice that are undergoing a chronic inflammatory response. The neoplasms are, at least in part, associated with insertional mutagenesis of the c-myb locus. Evidence is presented for the existence of at least two genetic elements of the virus that are crucial to induction of this disease but are not required for viral replication in hematopoietic tissues or induction of lymphoid disease. These genetic elements were detected by testing the pathogenicity of recombinants between Moloney and Friend MuLVs, the latter of which is nonleukemic to myeloid cells under these conditions, and by testing Moloney MuLV-based viruses that have nonretroviral sequences inserted at specific endonuclease sites in their long terminal repeats (LTRs). Analysis of the Moloney/Friend recombinants showed that there are sequences within the structural gene domain of Moloney, but not Friend, MuLV that are necessary for promonocytic leukemia, whereas the LTRs of the MuLVs are equally effective for promonocytic tumor formation and insertional mutagenesis of the c-myb gene. Experiments with viruses which were mutagenized in the LTR by insertions demonstrated that there is a specific genetic element in the U3 region of the LTR of Moloney MuLV, upstream of the 75-base-pair enhancer which, when interrupted, results in loss of leukemogenicity for cells in the monocytic lineage but not cells in the lymphoid lineage. We conclude, therefore, that promonocytic leukemia induction, in Moloney MuLV-infected mice undergoing a chronic inflammatory response, requires specific sequences in the structural gene region of Moloney MuLV as well as other sequences in the regulatory region of the virus.
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PMID:Regions of the Moloney murine leukemia virus genome specifically related to induction of promonocytic tumors. 240 39

The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon-modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c-fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species.
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PMID:Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non-coding (U)nA sequences. 335

The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activation observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analysed with the restriction enzymes Msp I and Hpa II, the c-myc locus of MCAQ 3-5 and MCAQ 1-4 was found hypomethylated as compared with that of the other cell lines tested that show low levels of c-myc transcripts. Our results suggest that one of the ways methylcholantrene could mediate transformation is by inducing an abnormal regulation of the c-myc gene.
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PMID:Increased transcription of the c-myc oncogene in two methylcholanthrene-induced quail fibroblastic cell lines. 609 23

R2 elements are non-LTR retrotransposons that insert in the 28S rRNA genes of arthropods. Partial sequence data from many species have previously suggested that these elements have been vertically inherited since the origin of this phylum. Here, we compare the complete sequences of nine R2 elements selected to represent the diversity of arthropods. All of the elements exhibited a uniform structure. Identification of their conserved sequence features, combined with our biochemical studies, allows us to make the following inferences concerning the retrotransposition mechanism of R2. While all R2 elements insert into the identical sequence of the 28S gene, it is only the location of the initial nick in the target DNA that is rigidly conserved across arthropods. Variation at the R2 5' junctions suggests that cleavage of the second strand of the target site is not conserved within or between species. The extreme 5' and 3' ends of the elements themselves are also poorly conserved, consistent with a target primed reverse transcription mechanism for attachment of the 3' end and a template switch model for the attachment of the 5' end. Comparison of the approximately 1,000-aa R2 ORF reveals that it can be divided into three domains. The central 450-aa domain can be folded by homology modeling into a tertiary structure resembling the fingers, palm, and thumb subdomains of retroviral reverse transcriptases. The carboxyl terminal end of the R2 protein appears to be the endonuclease domain, while the amino-terminal end contains zinc finger and c-myb-like DNA-binding motifs.
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PMID:The domain structure and retrotransposition mechanism of R2 elements are conserved throughout arthropods. 1033 Dec 76