Biomedical subjects

M Schorpp

Publications and source records attributed to M Schorpp.

23 records · Page 2Linked to original sources

PubMed1988

5'-flanking and 5'-proximal exon regions of the two Xenopus albumin genes. Deletion analysis of constitutive promoter function.

The 5'-flanking regions and the first two exons of the 68kd and 74kd albumin genes of Xenopus laevis reveal extensive sequence homology between the two in the exon part, in the 5'-flanking region up to position -400 as well as in the first intron. Sequence comparisons of the Xenopus genes with either the albumin genes of the chicken and mammals or the mammalian alpha-fetoprotein genes reveals no homology in the 5'-flanking region but some conserved features in the first exon. The analysis of the chromatin structure demonstrates a DNase I hypersensitive region in the promoter of the 68kd albumin gene specific for hepatocytes that express the albumin gene. Deletion analysis of albumin-CAT fusion genes indicates that a 69 base-pair fragment extending from -50 to +19 of the 68 kd albumin gene is sufficient for constitutive transcription in microinjected Xenopus oocytes. The addition of 5'-flanking sequences did not change the transcriptional activity. This is consistent with the sequence data that revealed no other promoter element in this region other than the TATA box. The absence of a CCAAT box distinguishes the Xenopus albumin genes from the mammalian albumin genes but is in agreement with the promoter structure of the alpha-fetoprotein genes.

Albumins↗

PubMed1986

An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells.

In the human breast cancer cell line MCF-7, we observe estrogen induction of the stable transfected Xenopus vitellogenin A2 gene. An estrogen-responsive element (ERE) could be defined by using a vitellogenin-chloramphenicol acetyltransferase hybrid gene in transient transfection experiments. The ERE is located in the 5' flanking region and is able to confer estrogen inducibility to the thymidine kinase gene promoter. By 5' and 3' deletions we have determined a 35 bp sequence sufficient for high stimulation by estradiol. Even 18 bp give a small estrogen response. The 35 bp ERE contains the palindromic sequence 5'GGTCACAGTGACC-3' as an essential element. The fact that the ERE of a frog gene functions in human cells demonstrates that signals and factors involved in the control have been conserved during evolution.

Acetyltransferases↗

PubMed1986

The mammalian genetic stress response.

A number of carcinogenic and cocarcinogenic agents induce new gene products in mammalian cells including primary human skin fibroblasts. These have been defined by cDNA cloning techniques, by protein resolutions in 2D PAGE and by the detection of new enzymatic functions. The uniform and transient genetic reaction is tentatively called the genetic stress response.

Animals↗

PubMed1986

Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts.

We used nucleic acid hybridization and cDNA cloning techniques to isolate human sequences that respond to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). These clones were used as probes to examine changes of gene expression that occurred after the proliferation of exponentially growing primary human fibroblasts was arrested. Transcript levels detected by these probes were increased coordinately by treatment of the cells with UV light, mitomycin C, TPA, or the UV light-induced extracellular protein synthesis-inducing factor EPIF (M. Schorpp, U. Mallick, H. J. Rahmsdorf, and P. Herrlich, Cell 37:861-868, 1984). Proteins coded for by these transcripts were characterized by hybrid-promoted translation and by cDNA sequencing. One of the cDNA clones was homologous to the metallothionein IIa gene, and one set of related clones selected RNA for the secreted TPA-inducible protein XHF1 (U. Mallick, H. J. Rahmsdorf, N. Yamamoto, H. Ponta, R.-D. Wegner, and P. Herrlich, Proc. Natl. Acad. Sci. USA 79:7886-7890, 1982).

Cell Transformation, Neoplastic↗

PubMed1984

UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells.

Ultraviolet light enhances the synthesis of at least eight abundant proteins in human fibroblasts within 2 hr. These proteins are identical with those induced by the tumor promoter TPA. The inducing signal is generated by DNA damage, as these proteins are induced by lower doses of UV in fibroblasts from patients with Cockayne's syndrome or Xeroderma pigmentosum. In the supernatant of UV-treated cells, a heat-labile ammonium sulfate precipitable factor of more than 10 kd (EPIF) was detected which, upon transfer to nonirradiated cells, mimicked UV in the UV-induced synthesis of gene products. The response to UV, TPA, or EPIF was inhibited by fluocinolone acetonide, but not by retinoic acid, protease inhibitors, or superoxide dismutase.

Cell Communication↗