Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a 12 kb clone from the murine genome which we show by DNA transfection studies to contain an entire functional L-myc gene and the transcriptional promoter sequences necessary for its expression. We have also isolated a 3.1 kb cDNA sequence from a murine brain cDNA library which corresponds to most of the L-myc mRNA. We have identified the L-myc coding region within the genomic clone by a combination of S1 nuclease analyses. Northern blotting analyses and comparative nucleotide sequence analyses with the cDNA clone. The L-myc gene appears to be organized similarly to the other well-characterized myc-family genes, c-myc and N-myc. The predicted amino acid coding sequence of the L-myc gene indicates that the L-myc protein is significantly smaller than c- and N-myc, but is highly related. In particular, comparison of the N- and c-myc protein sequences reveals seven relatively conserved regions interspersed among non-conserved regions; the L-myc gene retains five of these conserved regions but lacks two others. In addition, a portion of one highly conserved region is encoded within a different region of the L-myc gene but, due to changes in the size of L-myc exons relative to those of N- and c-myc, maintains its overall position in the peptide backbone with respect to other conserved regions. We discuss these findings in the context of potential functional domains and the possibility of overlapping and distinct activities of myc-family proteins.
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PMID:Structure and expression of the murine L-myc gene. 282 24

We studied N-myc RNA by in situ hybridization and S1 nuclease protection analysis in human fetal cerebrum, retina, lung, liver, and placenta during the second trimester. High levels of N-myc RNA were found in the early fetal cerebral germinal layer and the primordial cortex, with lower levels in the intermediate layer. After the twentieth week, N-myc expression declined in the attenuated germinal layer, remained high in the undifferentiated outer cortex, but declined in the differentiating inner cortex, which now expressed c-src. The primitive retina had high levels of N-myc RNA in the inner nuclear and ganglion cell layers between 12 and 21 weeks of fetal age. During this time, c-src RNA increased with fetal age in the ganglion cell layer. Lower levels of N-myc RNA were expressed in some cells of lung and placenta. Thus, appreciable N-myc RNA elevation is present in immature neural cells, disappears with differentiation, and may be unrelated to mitosis since high levels occur in the primordial cortex, which grows by accretion, and not by cell division.
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PMID:Expression of N-myc and c-src during the development of fetal human brain. 355 10

Neuroblastoma, the most common malignant solid cancer of children, has an ability to differentiate in vitro and in vivo. This biological property has a significant influence upon the prognosis of patients with neuroblastomas. Neuronal cells express three alternatively spliced forms of c-src mRNA (nonneuronal c-src, neuronal c-srcN1, and neuronal c-srcN2), which are found at different levels in adult and fetal human brain tissue. In this study, the transcriptional levels of the three c-src mRNAs were examined in relation to the neural differentiation in eight human neuroblastoma cell lines and two clonal sublines and in seven primary neuroblastoma tissues by S1 nuclease protection assays. Neuronal c-srcN1 mRNA was expressed at high levels in neuroblastoma cell lines with the ability to differentiate but not in the cell lines lacking the capacity to mature in response to chemical inducers irrespective of N-myc gene amplification and overexpression. In terminally differentiated neuroblastoma cells, the expression of neuronal c-srcN2 mRNA, which was barely detectable at a steady-state level in the uninduced cells, increased to significant levels. Infantile neuroblastomas identified by mass screening tests expressed both neuronal c-srcN1 and c-srcN2 mRNAs at levels almost identical to that found in human brain tissue, but terminally differentiated neuroblastoma cells, neuroblastomas from older children identified based on clinical symptoms, did not. These results suggest that neuronal c-src expression and the ability of neuroblastomas to differentiate in vitro and in vivo may be correlated.
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PMID:Expression of alternatively spliced src messenger RNAs related to neuronal differentiation in human neuroblastomas. 831 27

The myc gene family, including c- and N-myc, is believed to play a critical role in the regulation of cell cycle and proliferation. The function of N-myc, in contrast to c-myc, is not clearly understood. Here we report that, using a N-myc expression vector in CAT and S1 nuclease protection assays, the N-myc protein trans-represses expression of the human N-myc, the mouse N-myc, and the human MHC class 1 antigen genes. The analysis of N-myc deletion mutants showed that the N-terminal region where there are amino acid sequences highly conserved in the myc family and the central region where the acidic amino acids are concentrated, are necessary for trans-repression activity. Also, the region near the C-terminus is relevant for DNA-protein and protein-protein interaction; in particular, the basic region, helix-loop-helix, and leucine zipper are important for activity.
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PMID:Determination of transrepression domains of the human N-myc protein. 2158 77