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)

Deoxyribonucleic acid (DNA) polymerase activity was induced at approximately 18 to 20 hr after infection of secondary cultures of human embryonic kidney cells with adenovirus type 2 or type 12, and, at 30 to 50 hr after infection, the activity of this enzyme increased two- to threefold. The activity of thymidine kinase was also induced, but the activity of deoxycytidylic deaminase was not. The DNA content per cell at 71 hr after infection was 1.6-fold greater in adenovirus 2-infected cultures, and approximately 2.4-fold greater in adenovirus 12-infected cultures, than in the noninfected cultures. Several properties of DNA polymerase were studied. The enzymes in normal and adenovirus 2- or 12-infected cell extracts were saturated by approximately the same concentration of heat-denatured salmon sperm DNA primer (160 mug/ml); the enzyme activities had a similar broad pH optimum between 7.5 and 9. Extracts prepared from cells infected by either adenovirus did not activate DNA polymerase from noninfected cells, nor did the noninfected cell extracts inhibit enzyme activity of infected cell extracts. DNA polymerase in both normal and adenovirus 2- or 12-infected cells was located predominantly in the nucleus. In each case, the cytoplasm had only 30% of the enzyme activity of the nucleus. At 40 hr after infection with adenovirus 2 or 12, the activities of the enzyme in the nuclear and cytoplasmic fractions increased two- to threefold. Puromycin, an inhibitor of protein synthesis, prevented DNA polymerase induction when added to cultures during the 18- to 30-hr postinfection period, and it arrested the additional increase in enzyme activity when added after enzyme induction began. However, the increases in both DNA polymerase and thymidine kinase activities took place after treatment of infected cultures with 1-beta-d-arabinofuranosylcytosine, an inhibitor of DNA synthesis and adenovirus growth.
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PMID:Enhanced deoxyribonucleic acid polymerase activity in human embryonic kidney cultures infected with adenovirus 2 or 12. 574 41

The effect of testosterone propionate (TP) or estradiol-17 beta (E2) on the activities of thymidine kinase (TK) and tissue plasminogen activator (Act) in the prostates of 22 day old immature SD rats was studied. The Tailor and fibrin plate methods were applied to measure the activities of TK and Act respectively. Act activity was expressed in terms of the Urokinase International Unit. After a single TP injection im, TK activity began to increase at 24 h and peaked at 48 h followed by a rapid decrease. The maximum activity, 40.0 +/- 11.5 pmol/mg protein/15 min, was 50 times higher at 48 h and peaked at 96 h, with a subsequent decline to the control value within 14 days. The maximum Act activity, 5.1 +/- 0.4 U/prostate, was 1.6 times the control value. The activities of both TK and Act altered depending on TP doses, 1 mg/100 g BW of TP brought about their maximum activities at 48 h and 96 h respectively. Three TK isozymes were obtained from the prostates by DEAE-cellulose column chromatography. Fraction A, which was eluted in O M NaCl, differed from other isozymes in that its activity was only slightly suppressed by dCTP and was elevated most conspicuously after TP injection. Elevated activities of both TK and Act after TP injection were completely inhibited by Puromycin or Actinomycin D. The results of the present experiment demonstrated that TK and Act were synthesized in the prostate cells after TP injection and were androgen dependent. E2 did not inhibit the elevation of TK and Act activities by TP injection. In the present study estrogen showed a synergetic effect with androgen on these two activities, especially TK, in the rat prostate.
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PMID:[The effects of androgen and estrogen on thymidine kinase and tissue plasminogen activator in the prostate of immature rats (author's transl)]. 646 66

The in vitro differentiation of human induced pluripotent stem cells (hiPSC) to generate specific types of cells is inefficient, and the remaining undifferentiated cells may form teratomas. This raises safety concerns for clinical applications of hiPSC-derived cellular products. To improve the safety of hiPSC, we attempted to site-specifically insert a herpes simplex virus 1 thymidine kinase (HSV1-TK) suicide gene at the endogenous OCT4 (POU5F1) locus of hiPSC. Since the endogenous OCT4 promoter is active in undifferentiated cells only, we speculated that the HSV1-TK suicide gene will be transcribed in undifferentiated cells only and that the remaining undifferentiated cells can be depleted by treating them with the prodrug ganciclovir (GCV) prior to transplantation. To insert the HSV1-TK gene at the OCT4 locus, we cotransfected hiPSC with a pair of plasmids encoding an OCT4-specific zinc finger nuclease (ZFN) and a donor plasmid harboring a promoter-less transgene cassette consisting of HSV1-TK and puromycin resistance gene sequences, flanked by OCT4 gene sequences. Puromycin resistant clones were established and characterized regarding their sensitivity to GCV and the site of integration of the HSV1-TK/puromycin resistance gene cassette. Of the nine puromycin-resistant iPSC clones analyzed, three contained the HSV1-TK transgene at the OCT4 locus, but they were not sensitive to GCV. The other six clones were GCV-sensitive, but the TK gene was located at off-target sites. These TK-expressing hiPSC clones remained GCV sensitive for up to 90 days, indicating that TK transgene expression was stable. Possible reasons for our failed attempt to selectively target the OCT4 locus are discussed.
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PMID:Targeting of herpes simplex virus 1 thymidine kinase gene sequences into the OCT4 locus of human induced pluripotent stem cells. 2431 66