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 Drosophila gene for cyclin A is expressed in dividing cells throughout development. This expression pattern is similar to those of genes related to DNA replication, suggesting involvement of some common control mechanism(s). In the upstream region (-71 to -64 with respect to the transcription initiation site) of the CycA gene, we found a sequence identical to the DNA replication-related element (DRE; 5'-TATCGATA), which is important for high level expression of replication-related genes such as those encoding DNA polymerase alpha and proliferating cell nuclear antigen. Transient expression assays with chloramphenicol acetyltransferase (CAT) were carried out to examine the function of the DRE sequence of the CycA gene. Deletion or base substitution mutations resulted in an extensive reduction in CAT expression. Furthermore, monoclonal antibodies against DRE binding factor (DREF) diminished or supershifted the complex of the DREF and DRE-containing fragment. The results indicate that the Drosophila CycA gene is under the control of a DRE/DREF system, as are DNA replication-related genes.
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PMID:Transcriptional regulation of the Drosophila CycA gene by the DNA replication-related element (DRE) and DRE binding factor (DREF). 891 95

CTCF is a multifunctional transcription factor encoded by a novel candidate tumor suppressor gene (Filippova, G. N., Lindblom, A., Meinke, L. J., Klenova, E. M., Neiman, P. E., Collins, S. J., Doggett, N. D., and Lobanenkov, V. V. (1998) Genes Chromosomes Cancer 22, 26-36). We characterized genomic organization of the chicken CTCF (chCTCF) gene, and studied the chCTCF promoter. Genomic locus of chCTCF contains a GC-rich untranslated exon separated from seven coding exons by a long intron. The 2-kilobase pair region upstream of the major transcription start site contains a CpG island marked by a "Not-knot" that includes sequence motifs characteristic of a TATA-less promoter of housekeeping genes. When fused upstream of a reporter chloramphenicol acetyltransferase gene, it acts as a strong transcriptional promoter in transient transfection experiments. The minimal 180-base pair chCTCF promoter region that is fully sufficient to confer high level transcriptional activity to the reporter contains high affinity binding element for the transcription factor YY1. This element is strictly conserved in chicken, mouse, and human CTCF genes. Mutations in the core nucleotides of the YY1 element reduce transcriptional activity of the minimal chCTCF promoter, indicating that the conserved YY1-binding sequence is critical for transcriptional regulation of vertebrate CTCF genes. We also noted in the chCTCF promoter several elements previously characterized in cell cycle-regulated genes, including the "cell cycle-dependent element" and "cell cycle gene homology region" motifs shown to be important for S/G2-specific up-regulation of cdc25C, cdc2, cyclin A, and Plk (polo-like kinase) gene promoters. Presence of the cell cycle-dependent element/cell cycle gene homology region element suggested that chCTCF expression may be cell cycle-regulated. We show that both levels of the endogenous chCTCF mRNA, and the activity of the stably transfected chCTCF promoter constructs, increase in S/G2 cells.
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PMID:Characterization of the chicken CTCF genomic locus, and initial study of the cell cycle-regulated promoter of the gene. 975 95

It is widely assumed that mitotic cyclins are rapidly degraded during anaphase, leading to the inactivation of the cell cycle-dependent protein kinase Cdc2 and allowing exit from mitosis. The proteolysis of mitotic cyclins is ubiquitin/26S proteasome mediated and requires the presence of the destruction box motif at the N terminus of the proteins. As a first attempt to study cyclin proteolysis during the plant cell cycle, we investigated the stability of fusion proteins in which the N-terminal domains of an A-type and a B-type tobacco mitotic cyclin were fused in frame with the chloramphenicol acetyltransferase (CAT ) reporter gene and constitutively expressed in transformed tobacco BY2 cells. For both cyclin types, the N-terminal domains led the chimeric cyclin-CAT fusion proteins to oscillate in a cell cycle-specific manner. Mutations within the destruction box abolished cell cycle-specific proteolysis. Although both fusion proteins were degraded after metaphase, cyclin A-CAT proteolysis was turned off during S phase, whereas that of cyclin B-CAT was turned off only during the late G2 phase. Thus, we demonstrated that mitotic cyclins in plants are subjected to post-translational control (e.g., proteolysis). Moreover, we showed that the proteasome inhibitor MG132 blocks BY2 cells during metaphase in a reversible way. During this mitotic arrest, both cyclin-CAT fusion proteins remained stable.
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PMID:Cell cycle -dependent proteolysis in plants. Identification Of the destruction box pathway and metaphase arrest produced by the proteasome inhibitor mg132 983 45

Surfactant protein A (SP-A) is selectively synthesized in subsets of cells lining the respiratory epithelium, where its expression is regulated by various transcription factors including thyroid transcription factor-1 (TTF-1). Cell-specific transcription of the mouse SP-A promoter is mediated by binding of TTF-1 at four distinct cis-active sites located in the 5'-flanking region of the gene. Mutation of TTF-1-binding sites (TBE) 1, 3, and 4 in combination markedly decreased transcriptional activity of SP-A promoter-chloramphenicol acetyltransferase constructs containing SP-A gene sequences from -256 to +45. In contrast, the same mutations enhanced transcriptional activity in constructs containing additional 5' SP-A sequences from -399 to +45 suggesting that cis-acting elements within the region -399 to -256 influence effects of TTF-1 on SP-A promoter activity. A consensus Myb-binding site was identified within the region, located at positions -380 to -371 in the mouse gene. Mutation of the Myb-binding site decreased activity of SP-A promoter constructs in MLE-15 cells. MLE-15 cells, a cell line expressing SP-A mRNA, also expressed B-Myb. B-Myb bound to the MBS in the SP-A gene as assessed by electrophoretic mobility shift assay. While co-transfection of HeLa cells with a B-Myb expression plasmid activated the transfected SP-A promoter about 3-fold, co-transfection of B-myb with cyclin A and cdk-2, to enhance phosphorylation of B-Myb, increased transcriptional activity of SP-A constructs approximately 20-fold. Taken together, the data support activation of SP-A gene promoter activity by B-Myb which acts at a cis-acting element in the SP-A gene.
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PMID:Transcriptional regulation of the murine surfactant protein-A gene by B-Myb. 1048 87

We have followed Sp1 expression in primary human T lymphocytes induced, via CD2 plus CD28 costimulation, to sustained proliferation and subsequent return to quiescence. Binding of Sp1 to wheat germ agglutinin lectin was not modified following activation, indicating that the overall glycosylation of the protein was unchanged. Sp1 underwent, instead, a major dephosphorylation that correlated with cyclin A expression and, thus, with cell cycle progression. A similar change was observed in T cells that re-entered cell cycle following secondary interleukin-2 stimulation, as well as in serum-induced proliferating NIH/3T3 fibroblasts. Phosphatase 2A (PP2A) appears involved because 1) treatment of dividing cells with okadaic acid or cantharidin inhibited Sp1 dephosphorylation and 2) PP2A dephosphorylated Sp1 in vitro and strongly interacted with Sp1 in vivo. Sp1 dephosphorylation is likely to increase its transcriptional activity because PP2A overexpression potentiated Sp1 site-driven chloramphenicol acetyltransferase expression in dividing Kit225 T cells and okadaic acid reversed this effect. This increase might be mediated by a stronger affinity of dephosphorylated Sp1 for DNA, as illustrated by the reduced DNA occupancy by hyperphosphorylated Sp factors from cantharidin- or nocodazole-treated cells. Finally, Sp1 dephosphorylation appears to occur throughout cell cycle except for mitosis, a likely common feature to all cycling cells.
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PMID:Sp1 transcriptional activity is up-regulated by phosphatase 2A in dividing T lymphocytes. 1177 71

Platelet-rich plasma (PRP) is derived from fresh whole blood, which contains a high concentration of platelets. Recently, PRP has been used for skin wound healing and rejuvenation. However, the molecular mechanisms underlying PRP-inducing wound healing processes are still largely unknown. The aim of this study is to evaluate the effect of PRP on the expression of G1 cell cycle regulatory proteins, type I collagen, matrix metalloproteinase-1 (MMP-1), and MMP-2 in human skin fibroblasts (HSF). We performed a cell proliferation and a migration assay, immunoblotting, and a chloramphenicol acetyltransferase (CAT) assay in PRP-treated human skin fibroblasts. PRP treatment induced increased rates of cell proliferation and cell migration. Expression of cyclin A protein was increased by a low concentration (0.5%) of PRP-treated HSF. In addition, expression of Rb, cyclin E, and cyclin-dependent kinase 4 proteins was increased by a high concentration (5%) of PRP-treated HSF. High concentration of PRP induced an up-regulation of type I collagen, MMP-1, and MMP-2 expression in HSF. Taken together, PRP treatment induced an increase in expression of G1 cell cycle regulators, type I collagen and MMP-1, thereby accelerating the wound healing process.
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PMID:Platelet-rich plasma induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts. 2196 87

Application of autologous platelet-rich plasma (PRP) has been used for chronic wound healing. The aim of this study was to evaluate the effect of PRP on the wound healing processes of both acute and chronic ulcers and the underlying molecular mechanisms involved. We treated 16 patients affected by various acute and chronic ulcers with PRP. We performed molecular studies of cell proliferation, migration assays, immunoblotting and chloramphenicol acetyltransferase (CAT) assays in PRP-treated HaCaT keratinocyte cells. PRP treatment induced increased rates of cell proliferation and cell migration of HaCaT cells. In addition, the expression of cyclin A and cyclin dependent kinase (CDK) 4 proteins was markedly increased with a low concentration (0.5%) of PRP treatment in HaCaT cells. In 11 patients with chronic ulcers, including stasis ulcers, diabetic ulcers, venous leg ulcers, livedoid vasculitis, claw foot and traumatic ulcers, 9 patients showed 90-100% epithelization after 15.18 days. In 5 patients with acute ulcers, such as dehiscence, open wound and burn wound, 80-100% epithelization was achieved between 4 to 20 days. Topical application of PRP to acute and chronic skin ulcers significantly accelerated the epithelization process, likely through upregulation of the cell cycle regulatory proteins cyclin A and CDK4.
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PMID:Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells. 2324 28