Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterized a DNA-protein interaction within a sequence element distal from the site of transcription initiation within the mouse housekeeping gene (HPRT) promoter region. This interaction occurs within a 35-base pair regulatory element which confers cell type-specific gene transcription, designated as the HPRT cis-acting regulatory element (HCRE). Competition analysis by gel mobility shift electrophoresis indicates that this DNA-protein interaction is novel and not related to many transcription factors previously reported. Cell cycle synchronization experiments and gel mobility shift assays have demonstrated that within the HCRE a specific DNA-protein complex responds to G1 activation of the cell cycle. Experiments to purify specific DNA-binding proteins that interact with the HCRE has resulted in the purification of one sequence-specific DNA-binding protein of approximately 66 kDa. To determine the putative DNA-binding sequence, footprinting analysis has mapped the protection from DNase I hydrolysis which confers a core sequence of GTCTGGGT using both affinity purified protein and crude nuclear extract. This DNA motif represents a novel protein-binding sequence. Interestingly, data base searches have identified the same or homologous sequences of this DNA motif in additional genes, potentially related to cellular growth and proliferation. This consensus was most notable within a region 5' upstream of the ornithine decarboxylase gene. The unique cell type-specific regulation of the HPRT gene in the intestinal mucosa is not completely understood at this time but because of the relationship of ornithine decarboxylase expression to cell proliferation and more specifically, to mucosal cell renewal in the intestine, the function of DNA-protein interactions within the consensus sequence may prove analogous. This may account for the cell type-specific and cell-cycle responsive gene regulation previously demonstrated with HPRT. Identification of one sequence-specific DNA-binding protein within the HCRE suggest that this protein contributes to the trans-activation of specific genes during the immediate-early response of the cell cycle.
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PMID:Characterization of DNA-protein interactions within a distal regulatory element upstream of a mammalian housekeeping gene promoter. 155 10

The FtsH protein is an ATP-dependent cytoplasmic membrane protease involved in the control of membrane protein quality, cell division and heat shock response in Bacillus subtilis and many other bacteria. TilS, the tRNA(Ile2) lysidine synthetase, is a tRNA-binding protein that can modify pre-tRNA(Ile2). HprT, the hypoxanthine-guanine phosphoribosyltransferase, is implicated in purine salvage. Both tilS and hprT are essential for cell viability of B. subtilis. In this report, by co-purification experiments and gel filtration analyses, we show that there is complex formation between co-expressed TilS and HprT. Electrophoretic mobility shift assays and in vitro transcription analyses demonstrated that the TilS/HprT complex functions as a specific DNA-binding protein that can stimulate ftsH transcription in vitro. Two regions located upstream of the ftsH promoter have been identified as the TilS/HprT-binding sites and shown to be required for TilS/HprT-dependent ftsH transcription in vitro and in vivo. Results from gel supershift assays support the notion that the TilS/HprT complex likely employs its distinct segments for interaction with these two distinct TilS/HprT-binding sites, respectively. In conclusion, we present the first evidence that bi-functional TilS and HprT can form a complex to function as a transcriptional activator to stimulate ftsH transcription.
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PMID:Two enzymes, TilS and HprT, can form a complex to function as a transcriptional activator for the cell division protease gene ftsH in Bacillus subtilis. 2400 21