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L Tora

Publications and source records attributed to L Tora.

59 records · Page 4Linked to original sources

The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties.

We demonstrate here that the human oestrogen receptor (hER) cDNA clone pOR8 obtained from MCF-7 cells contains an artefactual point mutation which results in the substitution of a valine for a glycine at amino acid position 400 (Gly-400----Val-400). This mutation in the hormone binding domain of the cloned hER destabilizes its structure and decreases its apparent affinity for oestradiol at 25 degrees C, but not at 4 degrees C, when compared with the wild-type hER with a Gly-400.

Base Sequence↗

Cell-specific activity of a GGTCA half-palindromic oestrogen-responsive element in the chicken ovalbumin gene promoter.

Using a transient co-transfection system we have identified a functional oestrogen responsive element (ERE) in the near vicinity of the TATA box of the chicken ovalbumin gene promoter. Oestrogen induced activation of transcription was observed only in chicken embryo fibroblast cells, and not in human HeLa cells, suggesting the existence of a cell-specific transcription factor(s) that is necessary for the hormonal response. By 5'-deletion mapping and site-directed mutagenesis, a sequence encompassing the more proximal of two GGTCA half-palindromic motifs was identified as a functional ovalbumin gene ERE. Both motifs correspond to oestrogen receptor binding sites in vitro as revealed by DNase I footprinting. Optimal response to the hormonal stimulus apparently requires stereoalignment of the ERE and the TATA box.

Animals↗

The N-terminal region of the chicken progesterone receptor specifies target gene activation.

Steroid hormone receptors belong to a family of nuclear receptors that trigger transcriptional activation of target genes by specific binding to DNA recognition sequences, usually located in the 5'-flanking region of the target gene. Nuclear receptors appear to be segmented proteins and extensive structure-function analyses have attempted to elucidate the functional significance of individual segments. Two of these regions have been defined as the domains responsible for recognition of responsive elements of target genes (region C) and hormone binding (region E) (refs 2-7). But the functional significance of the N-terminal region (A/B), which diverges extensively even for a given receptor between different species, has remained obscure. We have previously cloned, expressed and analysed the chicken progesterone receptor (cPR) (ref. 8). This receptor and its human homologue from T47D breast cancer cells are unique among the steroid hormone receptors in that two forms, A and B, are present in equal amounts in cytosolic extracts, the latter having the higher molecular weight. For the chicken progesterone receptor, we have presented evidence suggesting that the cPR form A corresponds to an N-terminally truncated form of B (ref. 8). Here we report on the functional difference between the forms A and B in the transcriptional activation of two target genes.

Animals↗

Characterization of the L1NH repeat family of Novikoff hepatoma.

Long interspersed repeated sequences of the Novikoff hepatoma rat tumour cell genome were cloned and studied. No basic differences were found when the genomic organization of the Novikoff hepatoma was compared with that of other mammalian L1 families. The nucleotide sequence of the central approximately 4 kb (1 kb = 10(3) bases) part of the Novikoff hepatoma LINE (L1NH) appeared to be more highly conserved than the sequences found at the 5' and 3' ends. Moreover, the central approximately 4 kb core fragments were not always associated with the same end sequences. Thus, the occurrence of the more-conserved and more-abundant central portion in L1NH suggest that: (1) besides reverse transcription, other DNA- and/or RNA-mediated mechanisms might be involved in the dispersal of LINE families; and that (2) L1 sequences can sometimes consist of a compound unit made up of members of different L1 subunits and sequences with different genomic copy numbers.

Animals↗

Supercoil induced S1 hypersensitive sites in the rat and human ribosomal RNA genes.

Rat and human ribosomal RNA gene fragments in supercoiled plasmids were examined for S1 nuclease hypersensitivity. In the transcribed portion of genes the number and distribution of S1 sites were found to be species specific. No S1 sites were detected in the promoter regions. In the nontranscribed spacer (NTS), downstream of the 3' end of 28S RNA gene, S1 sites appear to be conserved in rat and human rDNAs. A rat NTS fragment (2987 nucleotides long), containing three S1 sites was sequenced and the S1 sites in this region were localized in polypyrimidine . polypurine simple repeat sequences. Other types of simple sequences, two type 2 Alu repeats and an ID sequence were also found in the sequenced region. The possible role of simple sequences and S1 sites in transcription and in recombination events of rDNA is discussed.

Animals↗