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)

CBP/tk, CCAAT Binding Protein for thymidine kinase, has been shown to bind to the distal and proximal CCAAT elements in human TK gene at G1/S boundary in normal human IMR-90 cells after serum stimulation (Pang and Chen, 1993). We now show that the serum-induced binding activity of CBP/tk was inversely related to the population doubling level (PDL) of the normal IMR-90 cells. However, little or almost no CBP/tk binding activity was observed in cells derived from patients with premature aging syndromes (e.g., Werner, Hutchinson-Gilford, and Cockayne syndrome). In contrast, CBP/tk binding activity in SV-40 virus-transformed human cells and in HeLa cells was overexpressed at levels 5- to 15-fold higher than that in normal cells and appeared to be deregulated. The half-life of CBP/tk binding activity in SV-40 transformed cells was at least 10 times longer than that in normal IMR-90 cells, suggesting that posttranslational control may contribute to the deregulation. CBP/tk binding activity detected in other mammalian cells such as murine NIH3T3, an immortal cell line, did not reveal any cell cycle dependence either. Further characterization of CBP/tk binding complex indicates that the binding complex may contain NF-YA and NF-YB and that the binding activity was sensitive to oxidizing reagents. Taken together, our data showed that the age- and cell cycle-dependent nature of CBP/tk is a function of cell types and that CBP/tk binding activity may be subjected to posttranslational and redox regulation.
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PMID:The age-dependent binding of CBP/tk, a CCAAT binding protein, is deregulated in transformed and immortalized mammalian cells but absent in premature aging cells. 870 9

Expression of thymidine kinase gene in normal human diploid cells is both cell cycle- and age-dependent and appears to be transcriptionally regulated. Strong DNA protein binding with a 28-bp fragment (-91/-64) that contains the distal inverted CCAAT box is observed in serum-stimulated young (low population doubling level) IMR-90 cells but not in senescent cells. This cell cycle- and age-dependent binding factor was termed CBP/ tk, indicating CCAAT binding protein for the thymidine kinase gene. Based on immunoshift assay and purification, it has been suggested that CBP/tk is equivalent to NF-Y, previously identified as the binding protein for the Y box within E alpha gene promoter. In this study, we examined the mRNA level and protein amount of NF-Y, proteins in young and old IMR-90 cells during serum stimulation by Northern and Western blot blot analyses. In addition, we compared (1) the turnover rate of NF-Y in IMR-90 cells with that of CBP/tk binding activity and (2) the levels of NF-Y and CBP/tk in normal and cancer cells. Both NF-YA and NF-YB were constitutively expressed at mRNA level in IMR-90 cells. However, expression of NF-YA, and to a lesser degree, NF-YB, at the protein level were clearly age-dependent. The half-life of NF-YA and NF-YB were, respectively, 4- and > 10-fold longer than that of CBP/tk binding activity in IMR-90 cells. In addition, we found that the amount of NF-Y did not correlate with the overexpression of CBP/tk binding activity in HeLa cells. Taken together, our results suggested that although CBP/tk may contain NF-YA or related proteins, NF-A and NF-YB alone may not account for all the characteristics of CBP/tk observed in normal and transformed human cells.
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PMID:Cell cycle- and age-dependent transcriptional regulation of human thymidine kinase gene: the role of NF-Y in the CBP/tk binding complex. 886 61