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Biomedical subjects

P Herrlich

Publications and source records attributed to P Herrlich.

At least 181 records · Page 10Linked to original sources
PubMed1983

Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene.

After transfection of mouse mammary tumor virus (MMTV) proviral DNA into cultured cells, the DNA is transcribed in a glucocorticoid-sensitive fashion. The large terminal repeat (LTR) region of MMTV is 1,328 nucleotides long and contains the regulatory information necessary for the hormonal response. We have constructed a MMTV LTR-thymidine kinase (tk) chimeric gene and have tested the biological activity of molecules containing various deletions in the LTR after transformation of LTK- APRT- mouse cells. In the TK+ transformants, both a LTR- tk chimeric RNA and an authentic tk RNA are correctly initiated and transcribed. The synthesis of the chimeric RNA as well as that of the tk RNA is hormonally regulated. A plasmid containing 202 nucleotides of LTR DNA 5' to the RNA initiation site is fully sensitive to glucocorticoids; 50 nucleotides still cause a residual inducibility.

Cell Transformation, Neoplastic↗
PubMed1983

A deletion mutant of mouse mammary tumour virus, lacking 516 nucleotides of the 5' long terminal repeat sequence, can be expressed in a hormone-responsive fashion.

In vitro manipulation of proviral DNA of mouse mammary tumour virus (MMTV) was used to construct mutants with defined deletions at the 5' end of the proviral gene. In the mutants 516, 1400 and 2000 nucleotides were removed from the 5' end. The deleted proviral DNA was tested for transcription and glucorticoid hormone regulation of viral RNA expression upon cotransfection into rat XC tk- cells with a thymidine kinase gene. Intact proviral DNA contained in the plasmid vector pBR322 and the deletion mutant pGR16 delta 516, missing 516 nucleotides of the 5' long terminal repeat (LTR) sequence, were transcribed in a hormone responsive fashion and produced RNA species of 35S and 24S. Deletion of the entire LTR sequence abolished MMTV transcription and the hormonal effect.

DNA, Viral↗
PubMed1982

Delimitation of a DNA sequence which confers inducibility by glucocorticoid hormones.

A chimeric long terminal repeat-thymidine kinase (LTR-tk) gene has been used to define the sequence requirements for glucocorticoid induction of gene expression. The original LTR-tk gene contains an entire mouse mammary tumor virus (MMTV) LTR preceding the tk gene. This gene can be expressed in a hormone-responsive fashion upon transfection into L tk--cells to produce a chimeric LTR-tk mRNA. Stepwise deletion of nucleotide sequences 5' of the viral RNA initiation site revealed that 202 nucleotides upstream of the viral cap site are sufficient for the hormonal regulation. Deletion of 5' sequences up to 59 nucleotides upstream of the viral cap site abolished RNA initiation in the LTR and hormonal induction.

Animals↗
PubMed1982

A B-lymphocyte-specific high-turnover protein: constitutive expression in resting B cells and induction of synthesis in proliferating cells.

A basic B-cell-specific protein of 35,000 daltons (XM1) is expressed at a high rate--comparable to actin--in resting splenic B lymphocytes of various species. Splenic or thymic T cells or fibroblasts do not express this protein. Upon polyclonal stimulation of B lymphocytes or in proliferating B-lymphocyte-derived cell lines, the synthesis of XM1 is switched off, but it is reinduced by agents that arrest replication, such as mitomycin C, hydroxyurea, ultraviolet light or gamma irradiation. Induction of XM1 after mutagen treatment is fast; the synthesis is regulated on the level of transcription or RNA processing. XM1 is turned over with half-life of less than 2 hr. XM1 is glycosylated. From compartment analysis and Triton solubilization it appears that XM1 is bound to the nuclear membrane.

Animals↗
PubMed1982

12-O-tetradecanoylphorbol 13-acetate-inducible proteins are synthesized at an increased rate in Bloom syndrome fibroblasts.

A set of proteins, which in normal fibroblasts were barely, if at all, detectable, were synthesized at an increased rate in fibroblasts from patients with Bloom syndrome (BS). The same set of proteins was induced in normal human fibroblasts by treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). In BS cells, TPA caused a further 2-fold increase in the rate of synthesis. Production of these proteins was inhibited by the addition of fluocinolone acetonide to the culture medium. One of the proteins (XHF1) present at high levels in BS fibroblasts and in TPA-treated cells was also induced by irradiation with ultraviolet light. This protein was secreted into the culture medium. Most other TPA-inducible proteins were cytoplasmic. Among other human mutants prone to chromosome aberrations we found one of three tested cases of Fanconi anemia and one case of ataxia-telangiectasia that showed increased spontaneous rates of synthesis of the TPA-inducible proteins. In these cases, however, the induction by TPA was like that seen in healthy fibroblasts.

Bloom Syndrome↗
PubMed1981

The endogenous proviral mouse mammary tumor virus genes of the GR mouse are not identical and only one corresponds to the exogenous virus.

The endogenous proviral copies of mouse mammary tumor virus (MMTV) were selected from a gene library of GR mouse DNA. We obtained five different lambda. MMTV recombinant clones. Four of them correspond to the 3' Eco RI fragments of the endogenous proviruses an one comprises an intact MMTV provirus with 2 to 3 kb of flanking mouse genomic DNA. Heteroduplex formation followed by S1 digestion under stringent conditions shows that there is nucleotide sequence heterology among the cloned endogenous proviral copies. Only one endogenous proviral copy, associated with the mtv-2 locus, was found to be totally homologous to the exogenous proviral DNA.

Animals↗
PubMed1979

Colivirus-T3-coded S-adenosylmethionine hydrolase.

Bacteriophage T3 induces an enzyme activity which hydrolyzes S-adenosylmethionine. This S-adenosylmethionine hydrolase is interesting, not only because of its unique activity, but also because the protein has to overcome host restriction [F. W. Studier and N. R. Movva (1976) J. Virol. 19, 136-145]. S-Adenosylmethionine hydrolase was purified to homogeneity using affinity chromatography on S-adenosylhomocysteine-Sepharose. The enzyme occurs in two forms, A and B. Form A consists of the viral peptide chain only; its native and subunit molecular weight is 17,000. Form B contains, in addition, a host subunit with a molecular weight of 49,000. The host subunit does not modify S-adenosylmethionine cleavage in vitro and no apparent relationship to the host-restriction system could be detected.

Bacterial Proteins↗
PubMed1979

A novel bacteriophage defence mechanism: the anti-restriction protein.

Bacteriophage T3 and T7 protect their DNA from restriction by producing, as the earliest detectable phage functions, anti-restriction proteins. Although the two phage proteins differ in their chromatographic and antigenic properties, they act by the same mechanism: the anti-restriction proteins inhibit E. coli K12 restriction endonuclease by direct interaction.

Coliphages↗
PubMed1979

Radiation sensitivity of messenger RNA.

Messenger RNA function is inactivated by irradiation with ultraviolet light. A unit length mRNA (in bases) is 2-3 times more sensitive than a unit length of DNA (in base pairs) with respect to the inactivation of template function. These data stem from four experimental systems all of which do not repair DNA: the translation of E. coli mRNA in rifampicin-treated cells, of T7 mRNA in infected E. coli, of f2 phage RNA in vivo, and of stable mRNA in chromosomeless minicells. The comparison of relative sensitivities to UV is relevant to the technique of UV mapping of transcription units which enjoys increasing popularity in pro- and eukaryotic genetic research.

DNA, Bacterial↗
PubMed1979

Export without proteolytic processing of inner and outer membrane proteins encoded by F sex factor tra cistrons in Escherichia coli minicells.

Most tra proteins encoded by the Escherichia coli F sex factor are incorporated into the minicell envelope. We have now assigned the tra proteins to cytoplasm (TraIp and 2b), inner membrane (TraEp, TraMp, and TraSp), and outer membrane (6e, TraAp, TraBp, TraJp, TraKp, TraLp, and TraTp). two proteins, TraDp and 6d, were associated with both inner and outer membranes. The proteins exported to the inner or outer membranes did not undergo proteolytic cleavage (processing) whereas beta-lactamase was processed normally.

Cell Membrane↗
PubMed1979

Regulation of synthesis of a major outer membrane protein: cyclic AMP represses Escherichia coli protein III synthesis.

Cyclic AMP is the effector molecule for both positive and negative control of synthesis of several Escherichia coli proteins. Among the latter is the major outer membrane protein III. The control mechanism occurs at the level of transcription and involves the cyclic AMP receptor protein. The repressing system is saturated at lower concentrations of cyclic AMP than is the positive control system.

Bacterial Proteins↗
PubMed1978

Nitrofurantoin damages DNA of human cells.

Nitrofurantoin causes damage to DNA of cultured diploid human fibroblasts. As a consequence DNA synthesis is blocked. The damage is removed by the normal enzymatic DNA repair system. Xeroderma pigmentosum fibroblasts which are defective in the excision endonuclease fail to repair nitrofurantoin-caused lesions.

DNA↗