Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter region of the liver/bone/ kidney-type alkaline phosphatase gene was examined to define the cis-acting regulatory sequences and transcription factors responsible for its expression in hematopoietic cells. Transient transfection experiments revealed that regions deleted up to -154 base pairs upstream from the transcription initiation site had significant activities to induce bacterial chloramphenicol acetyltransferase gene. The shortest DNA fragment was found to contain three GC boxes in addition to a TATA box. Electrophoretic mobility shift assay and Southwestern analysis showed that Sp3 could bind to the fragment. Western blot analysis also detected Sp3 protein in eluate from the DNA probe mixed with the nuclear extracts. Through the use of Drosophila Schneider cells that lack the Sp1 family of transcription factors, Sp3 was shown to activate the basal promoter in a dose-dependent manner. When the amount of Sp3 was limited, the most proximal GC box was found to be critical for the basal promoter activity.
 ...
PMID:Transcription factor Sp3 activates the liver/bone/kidney-type alkaline phosphatase promoter in hematopoietic cells. 1107 19

The binding of Sp1 transcription factor to DNA is considered a potential target for small ligands designed to interfere with gene transcription. We attempted to distinguish the direct inhibition of the Sp1-binding to DNA in vivo (cell culture) from more indirect effects due to the network of pathways that modulate cell cycle progression, which may decrease transcription without direct interference with Sp1-DNA interactions. We tested whether the Sp3 protein, whose putative binding sequence overlaps the Sp1 site, can inhibit Sp1-activated transcription and interfere with drug-DNA interactions. A well-characterized model system consisting of a wtGLUT1 (wild-type glucose transporter 1) gene promoter, or a mutated mut2GLUT1 promoter, linked to a CAT (chloramphenicol acetyltransferase) reporter gene, was used to analyze the effects of overexpressed Sp1 and Sp3 transcription factors in transiently transfected Jurkat T lymphocytes. Bisanthracycline WP631, a potent inhibitor of Sp1-activated transcription in vitro, was assayed for its ability to specifically inhibit transcription in transfected Jurkat T lymphocytes. The mut2GLUT1 promoter was used to further discriminate between the WP631 interference with Sp1-DNA complexes and Sp3-induced inhibition, since the Sp3-binding site is canceled in this promoter and replaced by a high-affinity binding site for WP631.
 ...
PMID:Sp1-targeted inhibition of gene transcription by WP631 in transfected lymphocytes. 1518