Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The JY328 clone was identified in a human genomic library using cDNA corresponding to mRNA for HLA-B7 as a probe. The L/328 cell line was established by cotransformation of mouse Ltk- cells with the herpes thymidine kinase gene and clone JY328. On Northern blots, RNA from L/328 strongly hybridized to an HLA class I probe, and an antigen was recognized by an anti-HLA class I framework antibody on the cell surface. A DNA probe corresponding to a segment of intron 7 was developed by comparing the nucleotide sequence of clone JY328 with that of other HLA class I-type genes. Using the radiolabeled probe to screen Southern blots of DNA from families with siblings exhibiting intra-HLA recombinations, a restriction fragment length polymorphism was revealed--a 1.4 kb BstE II band not present in all individuals. A corresponding fragment was apparent in the base sequence of clone JY328. The occurrence of this band on Southern blots established that JY328 maps distinct from and centromeric to the HLA-C locus and near to the HLA-B locus. Antibody absorption studies and cytotoxicity tests indicated that the JY328 gene product was not an HLA-B antigen but that it did specifically absorb CW7-specific antibody. In sum, these results suggest a novel, polymorphic HLA class I gene which expresses a product serologically similar to HLA-Cw7 but which does not map within the corresponding locus.
 ...
PMID:HLA-JY328: mapping studies and expression of a polymorphic HLA class I gene. 300 45

We isolated stable transformants of mouse L cells expressing human cell surface differentiation antigens by using immunofluorescence with monoclonal antibodies and selection with a fluorescence-activated cell sorter (FACS). Mouse L cells (TK-) were cotransformed with human cellular DNA and the herpes simplex virus thymidine kinase (TK) gene. TK+ transformants were first selected. The TK+ populations were stained with various fluorescent antibodies to membrane antigens, and positive cells were sorted and cloned by using a FACS. Transformants for HLA class I antigens, for beta 2-microglobulin, and for the T-cell differentiation antigens Leu-1 and Leu-2 were isolated. The frequency of antigen transformants among the TK+ transformants was about 0.5 X 10(-3). The sizes of the HLA, Leu-1, and Leu-2 molecules expressed by the transformants were the same as those of the proteins present on DNA-donor cells.
 ...
PMID:Stable transformation of mouse L cells for human membrane T-cell differentiation antigens, HLA and beta 2-microglobulin: selection by fluorescence-activated cell sorting. 618 54

To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.
 ...
PMID:A HLA class I cis-regulatory element whose activity can be modulated by hormones. 796 Feb 38

In augmenting systemic anti-tumor immune response, the authors evaluated the genetic modification of Ewing family tumor (EFT) cell lines for use as allogeneic vaccines. EFT cell lines A673 and RD-ES were transfected with cDNAs for human interleukin (IL)-2 and/or HSV1 thymidine kinase (HSV1-tk), respectively. Clones with high and stable secretion of IL-2 alone or with coexpression of functional HSV1-tk were obtained and their features were analyzed. IL-2 expressing clones derived from the A673 cell line demonstrated decreased expression of HLA class I molecules compared with the parental cell line and corresponding clones derived from RD-ES. However, IFN-gamma could upregulate the expression of HLA class I antigens by IL-2 transfected A673 cells. Ganciclovir induced apoptosis in double-transfected cell clones. IL-2/HSV1-tk cells continued to produce and release IL-2 after initial ganciclovir treatment. After gamma-irradiation, transfected clones released bioactive IL-2 in a quantity sufficient to activate T and natural killer cells in culture. A polyvalent allogeneic vaccine was also obtained using fusion of two different transgenic cell lines. The resulting hybrids inherited antigenic and transgenic characteristics of both parental cell lines. It is presumed that the cell lines generated here could be used as allogeneic vaccines for treatment of patients with EFTs.
 ...
PMID:Stable transgenic expression of IL-2 and HSV1-tk by single and fusion tumor cell lines bearing EWS/FLI-1 chimeric genes. 1255 23