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

We have isolated three overlapping genomic clones extending over 39 kilobases (kb), which encodes the rabbit cardiac sarco(endo)plasmic reticulum Ca2(+)-ATPase gene (SERCA2). S1 nuclease mapping and primer extension analysis of the 5' end of the cardiac/slow-twitch (SERCA2a) and smooth/non-muscle (SERCA2b) mRNAs showed that both transcripts are initiated from the same transcription initiation site, located 528 base pairs (bp) upstream of the translation initiation codon AUG. The putative promoter revealed a "TATA box" like element at -24 bp and a "CAAT box" at -78 bp relative to the cap site. A number of DNA sequence elements that could bind trans-acting factors were also found within the 1.8 kb of DNA sequence upstream from the transcription initiation site. To determine the DNA sequences governing transcriptional regulation, we have stably transfected the myogenic cell line C2C12 with a plasmid containing the putative promoter and 946 bp upstream sequence of the SERCA2 gene, coupled to the chloramphenicol acetyltransferase gene. Our results show that this chimeric plasmid construct exhibits appropriate activation and coordinate expression with the endogenous SERCA2 gene during the terminal differentiation of myoblasts into myotubes, suggesting that it contains the promoter and upstream sequence elements required for the regulated expression of the SERCA2 gene.
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PMID:Characterization of rabbit cardiac sarco(endo)plasmic reticulum Ca2(+)-ATPase gene. 213 26

The rabbit cardiac/slow twitch muscle sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2) gene encodes a Ca2+ transport pump whose expression is regulated during skeletal/cardiac muscle development and by different pathophysiological states of the heart. This study was designed to delineate cis-acting regulatory elements involved in SERCA2 gene expression. A series of unidirectionally deleted fragments of the upstream 1,460 bp SERCA2 promoter were linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Transient DNA transfection experiments performed with these constructs in C2C12 muscle cells and NIH3T3 fibroblasts revealed a 17 bp upstream promoter element (UPE) important for transcription of the SERCA2 gene in skeletal muscle cells. These studies have also identified a strong (muscle specific) negative regulatory region located upstream of nucleotide -658. Gel mobility shift and southwestern analyses using the 17 bp UPE have revealed a specific DNA binding complex referred to as Ca2+ ATPase promoter factor -1 (CaPF1). The binding factor has an approximate M(r) of 43 kDa. Comparison of CaPF1 with known transcription factors suggests that the CaPF1 complex may be a novel DNA-binding transcription factor which plays a role in SERCA2 gene regulation in vivo.
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PMID:Analysis of the rabbit cardiac/slow twitch muscle sarcoplasmic reticulum calcium ATPase (SERCA2) gene promoter. 833 69

Alterations in gene expression are a hallmark of cardiac hypertrophy and heart failure. Among these, the decreased expression of the sarcoplasmic reticulum calcium ATPase (SERCA2) has been described. Elevated levels of cytokines in particular, Leukemia Inhibitory Factor (LIF) and Interleukin-6 (IL-6) have been shown to have the capacity to elicit hypertrophic responses in cultured cardiac myocytes. In this study, we investigated the effects of these cytokines (LIF & IL-6) on the regulation of SERCA2 levels in cardiac myocytes. Cultured neonatal rat ventricular myocytes were transfected with a 3.2 kb promoter plasmid construct containing the SERCA2 promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene, and subsequently treated with 10 ng/ml LIF or 10 ng/ml IL-6. LIF and IL-6 independently caused a significant (p < or = 0.05) 23-36% inhibition in SERCA2 promoter activity. LIF and IL-6 induced inhibition was also evident in SERCA2 mRNA levels as assessed by Northern analysis. Time course of inhibition of SERCA2 mRNA levels showed the most prominent decrease occurring after 48 hours of treatment, with both cytokines having a dose dependent effect on the inhibitory response. Western analysis using a polyclonal antibody to SERCA2 protein indicate a significant, 60% decrease in the amount of total SERCA2 protein in cultured myocytes treated with 10 ng/ml LIF or IL-6. In conclusion, the cytokines LIF and IL-6 downregulate SERCA2 gene expression and protein levels. The molecular mechanism responsible for cytokine induced downregulation of SERCA2 is at least partly transcriptional.
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PMID:Leukemia Inhibitory Factor and Interleukin-6 downregulate sarcoplasmic reticulum Ca2+ ATPase (SERCA2) in cardiac myocytes. 1075 45