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 chicken ovalbumin gene is regulated at the level of transcription by four classes of steroid hormones. A steroid-dependent regulatory element (SDRE) found from -900 to -732 is required for this steroid-mediated induction. To define more precisely sequences of the SDRE required for steroidal induction, a series of exonuclease III deletions were made in the 3' end of the SDRE. Fusion genes containing the mutant ovalbumin 5'-flanking sequences linked to the chloramphenicol acetyltransferase structural gene (CAT) were transfected into steroid-responsive primary oviduct cells. These functional studies defined a region of the SDRE from -793 to -759 that is essential for induction by steroids. Analysis of protein interactions in this 34-base pair region by copper-phenanthroline footprinting and methylation interference assays defined nucleotides required for protein binding. Footprinting showed protection of residues extending from -784 to -765, an area that included nucleotides that, when methylated, interfered with protein binding. In addition, this footprinted region contained 10 nucleotides that were identical to sequences contained in the beta-interferon gene regulatory element. An oligomer synthesized to this region of homology produced two DNA-protein complexes with oviduct nuclear proteins. Although this region of the interferon gene regulatory element binds the transcription factor NF-kappa B, an oligomer from the immunoglobulin kappa light chain gene known to bind NF-kappa B did not compete with the SDRE oligomer for binding to oviduct nuclear proteins. Surprisingly, this same NF-kappa B oligomer was able to restore steroid responsiveness to an SDRE mutant, while an oligomer from the immunoglobulin heavy chain gene inserted in the same position did not affect induction by steroids. These data suggest that a protein binding to sequences in the SDRE that are similar to an NF-kappa B-binding site participates in the steroid-mediated increase in transcription of the chicken ovalbumin gene.
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PMID:A protein with a binding specificity similar to NF-kappa B binds to a steroid-dependent regulatory element in the ovalbumin gene. 203 95

The immunoglobulin kappa light chain gene contains a lymphoid-specific enhancer that includes several short protein-binding sequences. The sequence that binds the nuclear factor NF-kappa B was tested for its ability to act independently as an enhancer element by inserting it into test plasmids containing the chloramphenicol acetyltransferase gene. When analyzed for activity by transient transfection into lymphoid and nonlymphoid cells, a single copy of the NF-kappa B binding site could act as a tissue-specific upstream activating element. Two copies (dimer) showed 10-fold higher activity than did one copy and could act as an enhancer element 2.5 kilobases downstream of the transcriptional start site. The enhancer activity of this sequence was correlated with the presence of the cognate binding protein, NF-kappa B. This sequence acted as an inducible enhancer under conditions that induce NF-kappa B binding activity. Thus, the NF-kappa B binding site acts by itself as a tissue-specific and inducible enhancer element, and two copies show cooperative interaction.
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PMID:Oligonucleotide that binds nuclear factor NF-kappa B acts as a lymphoid-specific and inducible enhancer element. 312 49

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2)D3], a steroid hormone with immunomodulating properties, on nuclear factor kappa B (NF-kappa B) proteins was examined in in vitro activated normal human lymphocytes by Western blot analysis. Over a 72-hr period of activation, the expression of the 50-kDa NF-kappa B, p50, and its precursor, p105, was increased progressively. When cells were activated in the presence of 1,25(OH)2D3, the levels of the mature protein as well as its precursor were decreased. The effect of the hormone on the levels of p50 was demonstrable in the cytosolic and nuclear compartments; it required between 4 and 8 hr and was specific, as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were ineffective. Besides p50, 1,25(OH)2D3 decreased the levels of another NF-kappa B protein, namely c-rel. In addition, 1,25(OH)2D3 decreased the abundance of a specific DNA-protein complex formed upon incubation of nuclear extracts from activated lymphocytes with a labeled NF-kappa B DNA binding motif. Further, 1,25(OH)2D3 inhibited the transcriptional activity of NF-kappa B in Jurkat cells transiently transfected with a construct containing four tandem repeats of the NF-kappa B binding sequence of the immunoglobulin kappa light chain gene linked to the chloramphenicol acetyltransferase reporter gene. These observations demonstrate directly that there is de novo synthesis of NF-kappa B during human lymphocyte activation and suggest that this process is hormonally regulated.
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PMID:Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3. 747 23