Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that strong epitopes recognized by anti-Friend virus (FV) cytotoxic T lymphocytes (CTL) in H-2b mice are encoded in both the env and gag/pol regions of the helper friend leukemia virus genome. Two approaches have been used to identify these epitopes. At the nucleic acid level, we have constructed env genes with either of two in-frame deletions: pKR2, an env gene with a 681-bp deletion in the gp70 region and inserted into the pSV2-gpt-1 expression vector; and pKR1, an env gene with an 81-bp deletion in the p15E region and inserted into pSV2-gpt-1. Cell clones were established by transfecting Fisher rat embryo cells with pDb (the H-2Db restriction element), pNEO (for G418 selection) and either pKR1 or pKR2. Db and env gene expression was monitored by immunoprecipitation with polyclonal antibodies or by detection of viral RNA on Northern blots. Expressor cell clones were tested for susceptibility to lysis by polyclonal anti-FV/Db CTL in 51Cr-release assays. Whereas cells expressing pKR1 were lysed to the same extent as cells expressing the intact env gene, cells expressing pKR2 were resistant to lysis, suggesting that all detectable env epitopes are encoded within the 681-bp deletion. Polypeptides representing the two most likely candidate epitopes encoded in this segment were synthesized and tested for their abilities to sensitize FRE cells expressing Db alone for lysis by the CTL. One 17-mer polypeptide, AGTGDRLLNLVQGAYQA [corrected], functioned as a strong CTL epitope in this assay, but the other 18-mer polypeptide was inactive. Studies of the role of this epitope in the immune response to candidate viral vaccines are in progress.
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PMID:Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. 170 62

Transient transcription of the c-fos gene is induced by serum stimulation of quiescent cells during the earliest part of Gl phase, reaching maximum levels of mRNA within 30 min. To determine whether expression of c-fos is required, or has any regulatory role in continuous exponential cell proliferation following re-entry into the cell cycle, a chimeric plasmid was constructed containing the human c-fos gene such that transcription was under control of the SV40 promoter complex. The plasmid was co-transfected into HeLa S3 cells (RSfos cells) along with plasmids encoding pRSVcat and G418 resistance followed by clonal propagation. The regulatory role of c-fos in an exponentially growing transfected RSfos cell clone (CP17-14) and parental HeLa cells was assessed through studies of c-fos overexpression or suppression of c-fos translation by treatment with a c-fos antisense 16-mer oligonucleotide. Transfected cells grew normally despite excess expression of c-fos. In contrast, antisense oligonucleotide treatment efficiently suppressed proliferation in normal exponentially growing cells by more than 70% for approximately 60 hr. Beyond this time oligonucleotides were ineffective likely due to degradation/depletion. In contrast, transfected cells grew normally, indicating overexpression of c-fos was sufficient to neutralize the effects of c-fos antisense oligonucleotides. Flow cytometric analysis of cell cycle phase distribution and determination of proliferation rate in oligonucleotide treated HeLa cells revealed a virtually complete inhibition of cell proliferation without a block in any specific cell cycle phase. In addition, no effect of oligonucleotide treatment on cell cycle phase distribution was observed in CP17-14 cells. Overexpression of c-fos rendered these cells resistant as the antisense c-fos oligonucleotides were unable to impose proliferative inhibition. These results demonstrate that c-fos expression is required during all phases of the continuous cell cycle in exponentially growing cells suggesting an important maintenance role for c-fos in addition to its role during re-entry into the cell cycle from quiescence.
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PMID:c-fos expression is required during all phases of the cell cycle during exponential cell proliferation. 807 3