Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two small fragments of a novel human gammaherpesvirus genome known as Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (HHV-8) have been shown to be present in virtually all AIDS and non-AIDS KS lesions, as well as in body cavity-based lymphomas (BCBL) and in multicentric Castleman's disease. We have extended those studies by identifying and sequencing a third fragment of HHV-8 DNA encoding a viral thymidylate synthetase (TS) gene. Use of this viral TS fragment as a probe led to the identification and mapping of a cluster of overlapping phage lambda clones from a BCBL tumor DNA genomic library that spanned 48 kb on the left-hand side of the HHV-8 genome between the equivalents of open reading frame 6 (ORF6) and ORF31 of herpesvirus saimiri (HVS). DNA sequencing of a 17-kb segment encompassing a gammaherpesvirus divergent locus (DL-B) between ORF11 and ORF17 revealed the presence of nine viral ORFs with predicted gene products related to cellular proteins. These include the complete TS gene and a dihydrofolate reductase (DHFR) gene, four novel cytokine genes (encoding viral interleukin-6, viral MIP-1A, viral MIP-1B, and BCK) that have not previously been found to be encoded by a virus, and a bcl-2 homolog. This region in HHV-8 also contains the T1.1 abundant lytic cycle nuclear RNA gene and encompasses two genes (or exons) encoding proteins with C4HC3 zinc finger domains of the PHD/leukemia-associated protein subtype. The latter are related to the spliced immediate-early IE1 protein of the gamma-2 class herpesvirus bovine herpesvirus type 4 and a similar motif found in HVS ORF12. Although genes for TS and DHFR enzymes are also encoded by HVS (ORF70 and ORF2), both occur at different genomic loci than in HHV-8, and the HHV-8 DHFR protein is much farther diverged from human DHFR than is the HVS version, implying that they were probably acquired as host cell cDNAs by independent evolutionary events. Transcripts from the IE1-A, IE1-B, DHFR, and MIP-1B genes were all detected by Northern blot hybridization analysis in a BCBL cell line at 12 h after induction with butyrate but were not present before induction, indicating that these are all primarily lytic cycle genes. We conclude that the DL-B locus of gammaherpesviruses displays considerably more variability that previously appreciated and that expression of many of these genes is likely to have important implications for HHV-8 biology and therapy.
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PMID:A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins. 903 28

In sera of cachectic patients bearing advanced cancers, the concentration of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) have been reported to elevate. In this study, we investigated whether those cytokines influenced in vitro anti-tumor effect of 5-fluorouracil (5-FU) on a human colon tumor cell line, HCT-15. Pretreatment of HCT-15 cells with IL-1 beta, IL-6 or TNF-alpha did not affect the anti-tumor effect of 5-FU at various concentrations. However, IFN-gamma attenuated the anti-tumor effect of 5-FU at the concentrations of 0.1-10 IU/ml. An experiment with tritium thymidine showed that 0.1 IU/ml of IFN-gamma did not suppress the growth of HCT-15 cells. As low as 0.1 IU/ml of IFN-gamma attenuated the anti-tumor effect of 5-FU in another experimental system where HCT-15 cells were exposed to 0.1 IU/ml of IFN-gamma before and during the treatment with 5-FU. This system mimicked the clinical condition around in situ cancer cells. Treatment of HCT-15 cells with 0.1-10 IU/ml of IFN-gamma did not change their DNA histogram pattern. An immunoblotting with the antibodies to thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in HCT-15 cells revealed that 0.1-10 IU/ml of IFN-gamma enhanced their TS and DPD expressions. Results of the immunoblotting gave some explanation to attenuation in the sensitivity of HCT-15 cells to 5-FU.
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PMID:Serum factors attenuating the anti-tumor activity of 5-fluorouracil. 1160 2

We previously identified retroperitoneal fibromatosis-associated herpesvirus (RFHV) as a simian homolog of Kaposi's sarcoma-associated herpesvirus (KSHV) in a fibroproliferative malignancy of macaques that has similarities to Kaposi's sarcoma. In this report, we cloned 4.3 kb of divergent locus B (DL-B) flanking the DNA polymerase gene from two variants of RFHV from different species of macaque with a consensus degenerate hybrid oligonucleotide primer approach. Within the DL-B region of RFHV, viral homologs of the cellular interleukin-6, dihydrofolate reductase, and thymidylate synthase genes were identified, along with a homolog of the gammaherpesvirus open reading frame (ORF) 10. In addition, a homolog of the KSHV ORF K3, the modulator of immune recognition-1, was identified. Our data show a close similarity in sequence conservation, gene content, and genomic structure between RFHV and KSHV which strongly supports the grouping of these viral species within the same RV-1 rhadinovirus lineage and the hypothesis that RFHV is the macaque homolog of KSHV.
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PMID:Analysis of 4.3 kilobases of divergent locus B of macaque retroperitoneal fibromatosis-associated herpesvirus reveals a close similarity in gene sequence and genome organization to Kaposi's sarcoma-associated herpesvirus. 1269 11