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)

We have studied a panel of 10 genes and cDNA sequences that are expressed in a cell cycle-dependent manner in different types of cells from different species and that are inducible by different mitogens. These include five sequences (c-myc, 4F1, 2F1, 2A9, and KC-1) that are preferentially expressed in the early part of the G1 phase, three genes (ornithine decarboxylase, p53, and c-rasHa) preferentially expressed in middle or late G1, and two genes (thymidine kinase and histone H3) preferentially expressed in the S phase of the cell cycle. We have studied the expression of these genes in nonpermissive (tsAF8) and semipermissive (Swiss 3T3) cells infected with adenovirus type 2. Under the conditions of these experiments, adenovirus type 2 infection stimulates cellular DNA synthesis in both tsAF8 and 3T3 cells. However, four of the five early G1 genes (c-myc, 4F1, KC-1, and 2A9) and one of the late G1 genes (c-ras) are not induced by adenovirus infection, although they are strongly induced by serum. The other sequences (2F1, ornithine decarboxylase, p53, thymidine kinase, and histone H3) are activated by both adenovirus and serum. We conclude that the cell cycle-dependent genes activated by adenovirus 2 are a subset of the cell cycle-dependent genes activated by serum. The data suggest that the mechanisms by which serum and adenovirus induce cellular DNA synthesis are not identical.
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PMID:Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum. 242 24

The length of the prereplicative period after stimulation of quiescent WI-38 cells is prolonged in proportion to the length of time the cells are incubated prior to serum addition. Previous results from this laboratory have shown that this prolongation does not result from a delay in the induction of events which occur during the G0/G1 transition (i.e. c-fos or c-myc expression) (Owen, T., Cosenza, S., Soprano, D. R., and Soprano, K. J. (1987) J. Biol. Chem. 262 15111-15117). It was the goal of the present studies to examine the expression of other growth-associated genes known to be induced and maximally accumulate later in G1 to identify genes whose expression is coupled to entry into S rather than mitogenic stimulation. In order to do this, the temporal pattern of expression of a variety of growth-associated genes (thymidine kinase, p53, 2A9/calcyclin, ornithine decarboxylase, 4F1/vimentin, and c-Ha-ras) was studied in WI-38 cells stimulated either 12 days or 26 days after plating. We report that the time of induction and maximum accumulation of each of these transcripts, with the exception of c-Ha-ras, was delayed in the 26-day cell group for 10 h, a period of time approximately equal to the length of delay in entry of these cells into S. Thus the expression of these particular genes would appear to be closely coupled in time and sequence to the entry of cells into S. These results suggest that the prolongation of the prereplicative period in WI-38 cells is located in early G1, following the events leading to c-fos and c-myc induction but prior to the induction and maximum accumulation later in G1 of other growth-associated genes such as ornithine decarboxylase and 4F1/vimentin. In addition, these results provide molecular evidence for a definitive programmed order of gene expression during the progression of cells out of G0 through G1 to S.
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PMID:Evidence that the time of entry into S is determined by events occurring in early G1. 313 30

We previously demonstrated an enhancer-like positive regulatory element within a 259-bp sequence (-2352 to -2094 bp) of the human CYP1A2 gene in HepG2 cells. Three protein binding sites were identified by DNase I footprinting analyses within the 259-bp sequence: protected region A PRA; -2283 to -2243 bp), PRB (-2218 to -2187 bp), and PRC (-2124 to -2098 bp) (I. Chung and E. Bresnick, Mol. Pharmacol. 47, 677-685, 1995). In the present study, the functional significance of those protected regions was examined. Transfection experiments with deletion and substitution mutants defined the PRB and PRC as containing positive and negative regulatory elements, respectively. Human breast carcinoma MCF-7 cells were cotransfected with a hepatocyte nuclear factor-1 (HNF-1) expression vector and CYP1A2 promoter- or thymidine kinase promoter-luciferase reporter gene constructs. HNF-1, which contributes to the liver specificity of genes, enhanced reporter gene activity in a PRC sequence-dependent manner. These results suggested that PRC could exist bound to a repressor which was displaceable by other transcription factors such as HNF-1. Results obtained by transfection of HepG2 hepatoma cells with various PRB substitution mutant-luciferase gene fusion constructs indicated that the entire sequence of PRB was necessary for promoter activity. Consequently, the regulation of CYP1A2 expression is very complex, requiring a number of both positive and negative regulatory factors.
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PMID:Identification of positive and negative regulatory elements of the human cytochrome P4501A2 (CYP1A2) gene. 902 75