Thymidine kinase promoter

Diagram showing functional elements within the b-globin and thymidine-kinase promoters. The CAAT box in the thymidine-kinase promoter is in the opposite orientation relative to the transcriptional start site as compared to the CAAT... 

Herpes Simplex Virus Thymidine Kinase Promoter... 

Pelham, H.R.B. Bienz, M. (1982). A synthetic heat-shock promoter element confers heat-inducibility on the herpes simplex virus thymidine kinase gene. EM BO Journal, 1,1473-7. 

Other research groups are combining stress inducible promoters with the Cre-LoxP site specific recombination system of PI bacteriophage. Scott et al. (2000) have combined the ionizing radiation inducible EGR-1 promoter with this recombination system to express herpes simplex vims thymidine kinase (HSV-tk). With this combination system, radiation doses relevant for cancer treatment can be used to... 

The nuclear envelope acts as a permeability barrier for a variety of macromolecules, and DNA is no exception. In 1980, Mario Capecchi demonstrated that when a pBR322-derived plasmid expressing thymidine kinase (TK) was microinjected into the nuclei of TK-deficient mouse fibroblasts, between 50% and 100% of the injected cells showed TK activity at 24 hours post-injection (Capecchi, 1980). By contrast, in over 1000 cytoplasmically injected cells, no gene expression was detected in any cell during the same time frame. Similar results were obtained in another microinjection study using rat TK-deficient cells and a plasmid expressing chloramphenicol acetyl transferase (CAT) driven by a herpes TK promoter. When 1000-2000 copies of the plasmid were injected into the cytoplasm, less than 3% of the activity was seen as compared to cells injected in the nucleus with the same number of plasmids (Graessman et al., 1989). Zabner et al. 

A. Ido, K. Nakata, Y. Kato, K. Nakao, K. Murata, M. Fujita, N. Ishii, T. Tamaoki, H. Shiku, and S. Nagataki, Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter, Cancer Res. 55 3105 (1995). 

T. Joki, M. Nakamura, and T. Ohno, Activation of the radiosensitive EGR-1 promoter induces expression of the herpes simplex virus thymidine kinase gene and sensitivity of human glioma cells to ganciclovir, Hum. Gene Ther. 6 1507 (1995). 

M. W. R. Robertson, M. Wang, G. P. Siegal, M. Rosenfeld, R. S. N. Ashford, R. D. Alvarez, R. I. Garver, and D. T. Curiel, Use of a tissue-specific promoter for targeted expression of the herpes simplex virus thymidine kinase gene in cervical carcinoma cells, Cancer Gene Ther. 5 331 (1998). 

Although there is obviously a through-put such that [3H]dTTP is being formed and removed by DNA synthesis it appears that the size of the radioactive deoxythymidylate pool is determined by the concentration of extracellular thymidine (Fig. 12.2). This may come about by a combination of forward promotion of thymidine kinase by its substrate and feedback inhibition by dTTP (Ives et al., 1963). The size of the pool remains constant once equilibrium has been reached until extracellular thymidine levels begin to fall. This will happen within a few hours when the concentration of extracellular thymidine is 10-6M and even at 10-5 M 10% may be utilised within... 

In another study by Wang et al., i.v. injection of liposomes carrying rat insulin promoter (RIK)-thymidine kinase (TK) was found to be less toxic to the liver than the i.p. injection of the same formulation to severe combined immunodeficient mice (SCID) [192], The direct injection of the liposomes to abdominal cavity probably leads to higher local absorption and, thus, higher liver toxicity. In contrast, the i.v. injected volume is smaller (70 pL to 100pL of i.p. injection), which is diluted fast as soon as it enters the body. 

Rhee, K., Thompson, E. A. (1996) Glucocorticoid regulation of a transcription factor that binds an initiator-like element in the murine thymidine kinase (Tk-1) promoter. Molecular Endocrinol 10, 1536-1548. 

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