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 Rb family of proteins includes pRb, p107, and p130. These nuclear polypeptides associate with cyclins and transcription factors involved in the control of cell proliferation. This has suggested that members of the pRb family may modulate cell growth, at least in part, by regulating gene transcription. We have investigated the ability of p107 to modulate transcription and compared it with that of pRb. Whereas pRb inhibition of the c-myc promoter required the presence of E2F sites, p107 inhibition did not. Moreover, p107, but not pRb, repressed transcription from other promoters including fibronectin, herpes virus thymidine kinase, and a synthetic promoter containing a SV40 repeat activator motif upstream from the adenovirus major late-promoter TATA box. In contrast, the activity of the TATA-lacking promoters from the epidermal growth factor receptor and the cytoplasmic phospholipase A2 genes was unaffected by either p107 or pRb. Likewise, overexpression of p107 or pRb had no effect on the activity of a synthetic promoter lacking a TATA box and containing the SV40 repeat motif upstream from the terminal transferase gene initiator element. The domains in p107 required for transcriptional repression included the A segment of the pocket region and parts of the B segment, but not the spacer domain. In spite of their structural similarities, p107 and pRb may contribute to the control of cell proliferation by modulating the transcription of different genes.
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PMID:E2F-independent transcriptional repression by p107, a member of the retinoblastoma family of proteins. 775 78

We previously reported that the type II secreted phospholipase A2 (sPLA2) promoter from positions (-326 to +20) ([-326;+20] promoter) is negatively regulated by two adjacent regulatory elements, C (-210 to -176) and D (-247 to -210). This study examines in greater detail the way in which this negative regulation operates. Successive 5' deletions of the [-326;+20] type II sPLA2 promoter indicated that the region upstream of position -195 inhibits the transcription activity sixfold in HepG2 cells but not in HeLa cells. Although the whole [-326;-176] region decreased the activity of a heterologous thymidine kinase promoter, this effect was orientation and position sensitive. C/EBP beta, C/EBP alpha, and C/EBP delta, which bind to element C, prevented the inhibition of promoter activity. Electrophoretic mobility shift experiments identified the binding of NF1-like proteins to the [-225;-218] site, which overlaps an insulin response-like sequence, 5'-TGTTTTG-3'. This sequence bound a factor which also recognized the promoters of the apolipoproteins C-III and A-II. Substitutions preventing the binding of this factor or the NF1-like proteins did not increase the transcription activity, but substitution in the [-217;-204] sequence blocked the transcription inhibition. This sequence did not bind any double-strand binding factor, but its antisense strand is critical for the binding of single-strand binding proteins to the [-232;-191] region. We therefore suggest that these single-strand binding proteins are involved in the inhibitory mechanism.
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PMID:C/EBP factor suppression of inhibition of type II secreted phospholipase A2 promoter in HepG2 cells: possible role of single-strand binding proteins. 923 81

We propose that gene expression changes in accessible tissues such as blood often reflect those in inaccessible tissues, thus offering a convenient biomonitoring method to provide insight into the effects of environmental toxicants on such tissues. In this pilot study, gene expression changes in peripheral blood leukocytes (PBL) were compared to those in the uteri of adult rats to identify genes that were altered in both tissues following estradiol treatment. Ovariectomized rats were treated with either 17beta-estradiol or vehicle control (corn oil) for 3 days. PBL and uterine RNAs were hybridized to arrays containing 1185 genes. One hundred and ninety three genes were expressed in common between the PBL and uterus. Eighteen were changed significantly in both tissues, 9 of which were treatment- but not tissue-specific (e.g., jun-D, phospholipase A2, thymidine kinase). These results demonstrate that many genes are coexpressed between PBL and uterus, and that some are coregulated by estradiol. Given the limited number of genes examined in this study and the estimated size of other mammalian genomes, we conclude that many more genes will also be coregulated and suggest that accessible tissues such as PBL can serve as surrogate tissues for observing gene expression changes in inaccessible target tissues.
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PMID:DNA arrays to monitor gene expression in rat blood and uterus following 17beta-estradiol exposure: biomonitoring environmental effects using surrogate tissues. 1221 60