Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P13232 (Interleukin-7)
 580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The unintegrated closed circular form of viral DNA prepared from NIH3T3 cells infected with Kirsten murine sarcoma virus was cloned into bacterial plasmid pBR322. The closed circular DNA, which consisted of two different-sized populations, was enriched from the virus-infected cells, linearized with BamHI, and inserted into pBR322 DNA. Four different recombinant DNAs (clones 2, 4, 6, and 7) were obtained, and a physical map of each was constructed by using various restriction enzymes. Clone 4 DNA had the largest insertion, corresponding to a complete copy of the linear DNA. This suggested that this insertion contained two copies of the 0.55-kilobase pair long terminal redundant sequence. Clone 2 and clone 6 insertion DNAs had deletions of 0.2 and 0.5 kilobase pair, respectively, which mapped near the right end (3' side of viral RNA) of the linear DNA. Clone 7 DNA appeared to have a deletion of a single copy of the large terminal redundant sequence. Transfection of BALB3T3 cells with the clone 4 DNA insertion showed that this DNA had transforming activity. The efficiency of transfection with clone 4 Kirsten murine sarcoma virus DNA was enhanced eightfold by inserting EcoRI-cleaved viral DNA into the EcoRI site of pBR322. The EcoRI-inserted DNA produced foci with single-hit kinetics, suggesting that a single molecule of Kirsten murine sarcoma virus DNA can induce transformation. Results of transfections with EcoRI-inserted Kirsten murine sarcoma virus DNA cleaved with various restriction enzymes suggested that the first 3.3-kilobase pair region at the left end of the linear DNA is important for the initiation of transformation or maintenance of transformation or both.
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PMID:Structure and functions of the Kirsten murine sarcoma virus genome: molecular cloning of biologically active Kirsten murine sarcoma virus DNA. 626 39

It has been reported that SV40-transformed V 11 F 1 clone 1 subclone 7 rat cells (subclone 7) produce a super T antigen of 115,000 M. This super T antigen is entirely SV40 coded and is synthesized by translation of an elongated form of SV40 early mRNA (May, E., Kress, M. Daya-Grosjean, L., Monier, R. and May, P. (1981) J. Virol., 37, 24-35). The results reported here show that there is only one independent insertion of viral DNA in the cellular genome of subclone 7 cells. When DNA from subclone 7 cells was cleaved with Bam HI endonuclease two distinct SV40 sequence containing fragments were generated with sizes of 5 Kb and 10 Kb, respectively. Two recombinant cosmids were constructed by insertion of the 5 Kb and 10 Kb fragments, respectively, into cosmid pHC 79. Using restriction map analysis and nucleotide sequencing, we showed that the 5 Kb fragment actually contained the complete sequence of a gene encoding super T antigen. As compared to the normal SV40 early gene, the sequence of super T gene showed the following rearrangements: (i) The segment between nucleotides 4116 - 3544 was duplicated in a direct order and (ii) these two copies of 573 nucleotide sequence were separated by a 93 nucleotide tract which was a nearly perfect inverted repeat of the segment located between nucleotides 4868 and 4776 (nucleotide numbering used here = Weissmann number +17).
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PMID:Characterization of a gene encoding a 115 K super T antigen expressed by a SV40-transformed rat cell line. 627 94

To analyze the site of integration of the herpes simplex virus type I (HSV-I) thymidine kinase (TK) gene in biochemically transformed human cells, TK-HeLa-(BU25) cells were transformed to the TK+ phenotype by a cloned, 2 kbp Pvull fragment of HSV-I DNA. The transformed cells [HeLa(BU25)/TF pAGO PP3] were fused with mouse LM(TK-) cells, and human-mouse somatic cell hybrid clones (LH PP3 clones 1, 2, 3, 5 and 6) were isolated in HATG-ouabain selective medium. The HeLa(BU25)/TF pAGO PP3 cells and the LH PP3 hybrid clones expressed HSV-I specific TK activity and a herpesvirus-associated nuclear antigen, and contained herpesvirus nucleotide sequences. Molecular hybridization experiments were carried out to map the HSV-I and flanking cellular nucleotide sequences in the biochemically transformed cells. These experiments demonstrated that the HSV-I nucleotide sequences were integrated at a single site, and that the same cellular nucleotide sequences flanked the viral DNA in transformed HeLa(BU25)/TF pAGO PP3 and LH PP3 clone 5 cells. TK- revertant subclones isolated by growing the LH PP3 clone 5 cells in BrdUrd (and diphtheria toxin) failed to form colonies in HATG medium, but retained HSV-I nucleotide sequences. Isozyme analyses on 21 gene-enzyme systems representing 21 human chromosomes revealed that all of the LH PP3 clonal lines expressed human hexosaminidase B, which has been assigned to chromosome 5, and all were sensitive to diphtheria toxin, which is also a marker for chromosome 5. Chromosome analyses showed that chromosome 5 was the nly human chromosome present in mitoses of LH PP3 clone 5 cells and that human chromosome 5 was present in most of the mitoses of LH PP3 clone 1, 2, 3, and 6 cells. The latter clones also contained 1 or 2 additional human chromosomes in some of the cells. As expected from the molecular hybridization analyses, TK- revertants of LH PP3 clone 5 cells retained portions of chromosome 5 and expressed human hexosaminidase B. The results indicate that HSV-I nucleotide sequences were stably integrated in the biochemically transformed cells, most likely in human chromosome 5.
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PMID:The site of integration of the herpes simplex virus type 1 thymidine kinase gene in human cells transformed by an HSV-1 DNA fragment. 627 99

Classes of cell variants isolated from BALB/3T3-A31 clone 1 showing high, intermediate, and low susceptibility to ultraviolet light-induced transformation also demonstrated a differential response to benzo(a)pyrene (BP)-induced transformation. On the other hand, these variants showed an identical susceptibility to the killing effect of these carcinogens. The extent of BP binding to DNA was found to be very similar in all three classes of variants under transforming conditions. BP:DNA adducts from the variant cells were analyzed by high-pressure liquid chromatography. The same adducts (N2-(10S-[7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl)deoxyguanosine and a minute amount of the 7S enantiomer) were detected in the highly susceptible, the intermediately susceptible, and the resistant variant clones. Removal of the BP:DNA adduct occurred at an equally slow rate in all three classes of variant cells. These results indicate that the formation of stable covalent DNA adducts is not a sufficient condition for induction of transformation. Processes other than formation and removal of the stably bound BP:DNA covalent adducts are thus major factors controlling the susceptibility of BALB/3T3-A31 clone 1 variant cells to BP-induced transformation.
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PMID:Similarities in the formation and removal of covalent DNA adducts in benzo(a)pyrene-treated BALB/3T3 variant cells with different induced transformation frequencies. 628 45

Simian virus 40 (SV40) transformed V 11 F 1 clone 1 subclone 7 rat cells (subclone 7) do not synthesize normal-size large T antigen (M(r), 90,000); instead, they produce a 115,000 M(r) super T antigen (115K super T antigen). This super T antigen is SV40 virus coded, and its synthesis results from rearrangement and amplification of integrated viral DNA sequences in subclone 7 (May et al., Nucleic Acids Res. 9:4111-4128, 1981). In this study the functional activities of 115K super T antigen were compared with the functional activities of SV40 large T antigen. Transfection experiments were performed with (i) cosmid SVE 5 Kb and plasmid pSVsT, both containing the super T antigen gene and (ii) plasmids pSV1 and pSV40, both containing the large T antigen gene. Transfection of pSVsT DNA or SVE 5 Kb DNA into secondary cultures of rat kidney cells induced the formation of transformed cell foci with an efficiency that was about 50% of the efficiency of pSV1 DNA or pSV40 DNA. Concomitant with the transforming activity, two other activities were also retained by super T antigen, namely, the ability to enhance the level of host cellular protein p53 and the capacity to bind to p53. In contrast, pSVsT and SVE 5 Kb DNAs were markedly deficient in the capacity to support tsA58 DNA replication in CV1-P cells at a nonpermissive temperature (41 degrees C), as shown by cotransfection experiments. The yield of virus produced in these experiments was 400-fold less than the yield obtained in parallel experiments with pSV40 or pSV1. However, SVE 5 Kb and pSVsT have a functional SV40 replication origin, as shown by their efficient replication in COS 1 cells which provided functional large T antigen. Super T antigen also possesses a specific affinity for sequences of SV40 viral origin. Our results suggest that under certain conditions, evolutionary changes in T antigen take place and that these changes could be restricted to the phenotypic requirement of maintaining a structure that is able to induce cell transformation, to form a complex with p53, and to enhance the cellular level of p53. Therefore, there appears to be a close relationship among the activities of T antigen involved in transforming cells, in binding to p53, and in enhancing the p53 cellular level. Moreover, this set of activities appears to be separable from the replicative ability of T antigen, based on the observation that 115K super T antigen is markedly defective for initiating viral DNA synthesis.
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PMID:Study of the functional activities concomitantly retained by the 115,000 Mr super T antigen, an evolutionary variant of simian virus 40 large T antigen expressed in transformed rat cells. 630 Apr 61

We have previously cloned the gene encoding a 115,000-Mr super T antigen (115K super T antigen), an elongated form of the Simian virus 40 large T antigen, originating from the rat cell line V 11 F1 clone 1, subclone 7 (May et al., J. Virol. 45:901-913, 1983). DNA sequence analysis has shown that the 115K super T antigen gene contains notably an in-phase duplication of a sequence located in the region of tsA mutations. We have also shown that the 115K super T antigen gene is able to induce the formation of transformed foci in transfected rat cells. After rat cell cultures were transfected with the cloned gene encoding 115K super T antigen, we obtained a large number of transformants as reported in this paper. In these transformants, we detected a very high frequency of new T antigen variants, as shown by immunoprecipitation of the cell extracts with anti-simian virus 40 tumor serum followed by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Based on these results and all of the data presently available, it appears likely that the input plasmid or cosmid DNAs containing the cloned gene were first subjected to recombination events that yield new variant T antigen genes before these recombinant genes become integrated. The new variant T antigens observed in the transformants were predominantly those comigrating with normal-size large T antigen. In fact, these latter variants appeared to be indistinguishable from wild-type large T antigen as judged by restriction mapping by Southern blotting of the total genomic DNA of the transformants. Models of intermolecular or intramolecular homologous recombination occurring between or within the input plasmid or input cosmid DNA molecules are proposed to account for the formation of such revertants.
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PMID:Conversion through homologous recombination of the gene encoding Simian virus 40 115,000-molecular-weight super T antigen to a gene encoding a normal-size large T antigen variant. 633 May 31

A diverse range of ultimate chemical carcinogens inhibited the transfer of methyl groups from S-adenosylmethionine to hemimethylated DNA in a reaction catalyzed by mouse spleen methyltransferase. The formation of alkali-labile sites in DNA lessened its ability to accept methyl groups in vitro, but the methylation reaction was much less sensitive to thymine dimers or double-strand breaks. Carcinogens induced the formation of alkali-labile DNA lesions, but the degree of methyltransferase inhibition observed was greater than that expected for this damage alone. Certain carcinogens were also capable of direct modification and inactivation of the methyltransferase enzyme. Benzo(a)pyrene treatment of living BALB/3T3 A31 clone 1-13 but not C3H/10T1/2 clone 8 cells resulted in a 12% decrease in total 5-methylcytosine content of cellular DNA. Carcinogenic agents may therefore cause heritable changes in 5-methylcytosine patterns in certain cell types by a variety of mechanisms, including adduct formation, induction of apurinic sites and single-strand breaks and direct inactivation of DNA methyltransferase.
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PMID:Inhibition of DNA methylation by chemical carcinogens in vitro. 682 70

The effect of sodium fluoride on the growth of two continuous human cell lines, i.e. HeLa cells and human conjunctiva clone 1-5C-4 cells, was studied. The growth of HeLa cells and clone 1-5C-4 cells was arrested nearly completely by the addition of 0.95 and 1,90 mM of sodium fluoride, respectively. DNA synthesis in HeLa cells, determined by incorporation of 3H-thymidine, was not affected appreciably for the first 24-hr period after the addition of sodium fluoride. Markedly reduced incorporation, however, occurred during the next 24-hr period. Thus, there was a discrepancy between the immediate cessation of cell division and the delayed suppression of DNA synthesis. On the other hand, a suppressive effect of sodium fluoride on protein synthesis determined by 14C-leucine incorporation was evident already during the first 24-hr period. The results indicate that the inhibition of protein synthesis is the main cause of growth inhibition.
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PMID:The effects of fluoride on cell growth of two human cell lines and on DNA and protein synthesis in HeLa cells. 683 27

A normal rat cell line, 3Y1-B clone 1-6 (3Y1) and its adenovirus (Ad) type-12-transformed derivatives, W4 (transformed by Ad12 Virion), WY3 (transformed by Ad12 whole DNA), CY1-1 (transformed by the Ad12 EcoRI-C fragment, left 16.5%), GY1-1 (transformed by the Ad12 HindIII-G fragment, left 6.8%) and HY1 (transformed by the Ad12 Acd-H fragment, left 4.7%) were studied cytogenetically. 3Y1 and some of the transformed cell lines (W4, WY3 and GY1-1) were diploid or pseudodiploid, while others (CY1-1 and HY1) were hypotetraploid. A metacentric marker M1 was detected in GY1-1 cells and another marker M2 in W4 and CY1-1 cells at a high frequency. By the Giemsa banding technique, the metacentric markers M1 and M2 from these fully transformed cell lines were identified as isochromosomes derived from 1q (M1) and 3q (M2), respectively. On the other hand, the markers were detected only at a low frequency in incompletely transformed HY1 cells. However, hypersomy in chromosome No. 1 was observed at a high frequency in this cell line. It can be concluded that hypersomy of chromosomes No. 1 or 3 found in transformants and metacentric markers found in complete transformants are characteristic features in rat cells transformed by Ad12.
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PMID:Chromosomal alterations of rat cell lines transformed by human adenovirus type-12 virion, whole DNA and left-end DNA fragments. 725 Dec 22

12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid] is a lipoxygenase metabolite of arachidonic acid. Treatment of murine-lung-derived microvascular endothelial cells (CD clone 4) with exogenous 12(S)-HETE promoted wound healing of injured endothelial cell monolayers. 12(S)-HETE, in a time- and dose-dependent manner, enhanced the growth of CD clone 4 cells. Thymidine incorporation assays demonstrated that 12(S)-HETE increased the DNA synthesis by > 4 fold. In addition, normal endothelial cell growth stimulated by serum could be dose-dependently inhibited by a select 12-lipoxygenase inhibitor (BHPP), suggesting that 12(S)-HETE is a physiological mitogenic factor for microvascular endothelial cells.
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PMID:12(S)-HETE is a mitogenic factor for microvascular endothelial cells: its potential role in angiogenesis. 754 Aug 38


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