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)

We have isolated a genomic clone containing the mouse neu gene. The 5' end of the mouse neu gene was localized by Southern analysis, subcloned and characterized. DNA sequence analysis revealed that the promoter region is 67% G+C-rich and lacks a TATA box, although a CAAT box is present. By sequence comparison, we identified several consensus recognition sequences for general transcription factors such as Sp1, E4TF1, AP2, OTF-1 and GCF, as well as recognition sequences for RVF, E1A and GTG, which have recently been identified in the rat neu promoter. Functional promoter activity was demonstrated by the ability of the promoter to drive transcription of the bacterial chloramphenicol acetyltransferase gene. Using a series of 5'-end deletion mutants, we have identified multiple positive and negative cis-acting elements that regulate mouse neu gene transcription.
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PMID:Cloning and characterization of the mouse neu promoter. 134 55

The previously reported nucleotide sequence of the spoOA coding region of Bacillus subtilis suggested that the protein is initiated with either of two possible initiation codons, ATG and GTG, 84 base pairs apart. To determine which codon is utilized as an initiator in B. subtilis, we constructed a fusion gene in which the promoter and NH2-terminal region of the spoOA gene was connected to the chloramphenicol acetyltransferase gene (cat gene). After introduction of the plasmid carrying the spoOA-cat fusion gene into B. subtilis cells, the fusion protein was purified by affinity chromatography. The sequence of NH2-terminal amino acids of the fusion protein was determined and the result established that the GTG codon is utilized as an initiator in B. subtilis. Comparison of the amino acid sequences revealed a marked homology between the spoOA (NH2-terminal half) and spoOF proteins. A less striking but significant homology was also found between the spoOA (COOH-terminal half) and spoOB proteins. This suggests the presence of a common functional domain structure for these proteins that are supposed to play key regulatory roles in sporulation.
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PMID:Amino-terminal structure of spoOA protein and sequence homology with spoOF and spoOB proteins. 301 27

Mutations of the human androgen receptor gene were identified in five subjects from four families with androgen insensitivity syndrome. Individual exons of the androgen receptor gene were amplified by the polymerase chain reaction from genomic DNA and screened for sequence-dependent differences in their melting characteristics by denaturing gradient gel electrophoresis. DNA fragments from exons with altered mobility were sequenced. Four different single nucleotide base substitutions were found within exons 5, 6, and 7 encoding the steroid-binding domain of the androgen receptor. In one subject with ambiguous genitalia, amino acid residue 763 was changed from tyrosine to cysteine (TAC-->TGC; Y763C). Four subjects, including two siblings, had complete androgen insensitivity. In one subject, residue 779 was changed from arginine to tryptophan (CGC-->TGG; R779W), another subject (M807V) had a substitution of valine (GTG) for methionine (ATG) residue at position 807, and the two siblings (R855C) had a mutation in residue 855 changing arginine (CGC) to cysteine (TGC). Binding of the synthetic androgen ligand, methyltrienolone (R1881), by the mutant receptor Y763C was decreased by 54% compared to the normal receptor. Transcriptional activation of a mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter gene by AR mutant Y763C was negligible at 0.1 nM R1881 and only 55% at 10 nM R1881 when compared to the maximal response with the normal AR, as assessed by CAT activity. Mutant M807V retained only 22% of normal R1881 binding and mutant R855C was unable to bind the steroid. In accordance with the steroid binding, transcriptional activation of MMTV-CAT by M807V rose to only 26% of control in the presence of 10 nM R1881, a concentration at which R855C remained functionally inactive. In summary, missense mutations within the exons of the androgen receptor gene encoding the steroid-binding domain of the receptor are common causes of both partial and complete forms of androgen insensitivity syndrome.
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PMID:Human androgen insensitivity due to point mutations encoding amino acid substitutions in the androgen receptor steroid-binding domain. 758 99

The androgen receptor (AR) from a patient with Reifenstein syndrome (incomplete androgen insensitivity syndrome) was characterized. The patient's pubic skin fibroblasts had normal androgen binding. However, when incubated at 41 C, fibroblasts from the patient had a marked decrease in androgen binding as compared with normal fibroblasts. Analysis of coding sequences of the androgen receptor gene revealed a single nucleotide substitution in exon E, resulting in an amino acid change from glycine (GGG) to valine (GTG) at amino acid 743 within the steroid binding domain of AR. Reconstruction of this mutation by site-directed mutagenesis into a human AR complementary DNA followed by expression in COS1 cells led to production of a mutant AR with no significant difference in androgen binding when cells were incubated with androgen at room temperature. However, in contrast to wild type AR expressed in COS1 cells, the mutant AR had markedly lower androgen-binding affinity at 41 C. The mutant receptor could still stimulate a reporter gene at 37 C but this transcriptional stimulation was also decreased when compared with wild type AR receptor in a chloramphenicol acetyltransferase assay. These results suggest that partial androgen resistance in this patient with Reifenstein syndrome is due to a single point mutation in the steroid binding domain of the androgen receptor.
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PMID:A single amino acid substitution (gly743 --> val) in the steroid-binding domain of the human androgen receptor leads to Reifenstein syndrome. 832 32

The mouse cytochrome oxidase (COX) Vb promoter contains three sequence motifs with partial or full consensus for YY-1 and GTG factor binding and a CArG box, located between positions -480 and -390. Individually, all three motifs stimulated transcription of the TKCAT promoter, and bound distinctly different proteins from the liver and differentiated C2C12 nuclear extracts. Collectively, these motifs, together with the downstream flanking sequence, -378 to -320, suppressed the transcription activity of heterologous promoters, thymidine kinase-chloramphenicol acetyltransferase (TKCAT) and COXIV/CAT. The transcription activities of both TKCAT and COXIV/CAT constructs were induced 3-4-fold during induced myogenesis of C2C12 cells. The downstream CArG-like motif binds transcription factor YY-1, while the upstream YY-1-like motif binds to a yet unidentified factor. Co-expression with intact YY-1, but not that lacking the DNA binding domain suppressed the transcriptional activity. Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation. Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissues.
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PMID:Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis. Role of a YY-1 factor-binding negative enhancer. 903 8

To determine the molecular mechanism of regulation of pentylenetetrazol (PTZ)-induced calcium entry by the seizure-related gene, PTZ-17, the role of the 3'-untranslated region (3'UTR) and also interaction between 3'UTR and intracellular factors were investigated. PTZ-induced calcium inward current in Xenopus oocytes injected with PTZ-17 RNA varied in magnitude among strains of mice: RNA derived from the DBA/2 mouse, which has a high susceptibility to convulsions, showed the largest current and that from the BALB/c mouse with a low susceptibility to convulsions showed no PTZ response. The sequence of 3'UTR showed alterations among mouse strains: 3'UTR of BALB/c showed a sequence alteration from T to G and that of DBA/2 showed a GTG insertion compared with that of B6. The 3'UTR also regulated the translation of chloramphenicol acetyltransferase (CAT) RNA depending on its sequence. A particular region within the 3'UTR demonstrated interaction with 60- and 47-kDa proteins. Sequence alterations in this region corresponded to disappearance or increase in PTZ-induced calcium entry. These findings suggest that a particular region within 3'UTR of the seizure-related gene, PTZ-17, is involved in PTZ-induced calcium entry via interaction between mRNA and specific RNA-binding proteins.
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PMID:Molecular mechanism of regulation of pentylenetetrazol-induced calcium entry by 3'-untranslated region of a seizure-related cDNA, PTZ-17, in Xenopus oocytes. 922 1