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D S Latchman

Publications and source records attributed to D S Latchman.

At least 289 records · Page 16Linked to original sources
PubMed1991

The constitutively expressed octamer binding protein OTF-1 and a novel octamer binding protein expressed specifically in cervical cells bind to an octamer-related sequence in the human papillomavirus 16 enhancer.

A novel octamer binding protein expressed specifically in cervical cells but not in other cell types has been identified. This protein differs in size and sequence specificity from the constitutively expressed octamer binding protein OTF-1. In particular it binds with higher affinity to a sequence in the human papillomavirus 16 (HPV) upstream regulatory region which has a seven out of eight base pair match compared to the consensus octamer motif. This is the first example of a tissue specific protein which has been observed to bind to the papillomavirus enhancer. The possible role of this protein in producing the observed tissue specific activity of the enhancer and in cervical carcinogenesis induced by HPV is discussed.

Base Sequence↗
PubMed1991

Differential expression of the mouse U1a and U1b SnRNA genes is not dependent on sequence differences in the octamer motif.

The mouse U1b SnRNA gene is expressed in only a limited range of cell types, whereas the U1a SnRNA gene is expressed in all cells. These two genes differ in the sequence of the octamer motif, which plays a critical role in SnRNA gene regulation. We show that the U1b octamer binds the octamer-binding protein Oct-1 with higher affinity than does the U1a octamer in both U1b-expressing and -non-expressing cell lines and tissues. Moreover, the U1b octamer can direct a higher level of gene expression than the U1a octamer when linked to a heterologous promoter and introduced into a non-U1b-expressing cell line. Hence the tissue-specific expression of the U1b gene is not determined by the failure of its octamer motif to bind Oct-1 or the weak affinity of this binding.

Animals↗
PubMed1991

The overlapping octamer/TAATGARAT motif is a high-affinity binding site for the cellular transcription factors Oct-1 and Oct-2.

The octamer motif in cellular promoters and the related TAATGARAT element in the herpes simplex virus (HSV) immediate-early promoters can both bind cellular octamer-binding proteins. The overlapping octamer/TAATGARAT elements (consensus ATGCTAATGARAT) found in the HSV-1 IE1 promoter thus represent a composite motif, each portion of which can independently bind octamer-binding protein. By comparing the binding characteristics of this composite motif with its individual elements, we show that it binds a single molecule of either Oct-1 or Oct-2 with much higher affinity than does either an octamer or TAATGARAT motif alone. This strong binding allows this element to direct a much higher level of gene expression when linked to a heterologous promoter than that observed with each of its individual components.

Base Sequence↗
PubMed1991

The herpes simplex virus virion protein Vmw65 transcriptionally activates the gene encoding the U4 snRNA but not that encoding the U2 snRNA during lytic infection.

Although lytic infection with herpes simplex virus (HSV) causes the repression of most host cell biosynthesis, it results in increased transcription of the cellular gene encoding the U4 snRNA, leading to accumulation of this snRNA. In contrast, no increased transcription of the gene encoding the U2 snRNA or accumulation of this RNA is observed in infected cells. These effects are mediated by the HSV virion protein Vmw65, which activates the U4 gene but does not affect the U2 gene. The significance of this difference between the U2 and U4 genes is discussed with regard to the presence in both of these genes of an identical octamer-binding site for the cellular transcription factor Oct-1 which complexes with Vmw65.

Animals↗
PubMed1991

Heat-shock proteins.

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Antibodies, Bacterial↗
PubMed1991

A cellular factor binding to the TAATGARAT DNA sequence prevents the expression of the HSV immediate-early genes following infection of nonpermissive cell lines derived from dorsal root ganglion neurons.

Cell lines derived from dorsal root ganglion neurons are nonpermissive for HSV infection and do not transcribe the viral immediate-early genes following infection. The lack of immediate-early gene transcription in these cells is caused by the presence of a neuronal cell specific inhibitory factor which binds to the TAATGARAT elements in the promoters of these genes and prevents their transcription. The significance of these results for an understanding of the processes regulating the interaction of HSV with neuronal cell types and the establishment of latent infections in vivo is discussed.

Animals↗
PubMed1991

The 90-kDa heat shock protein protects mammalian cells from thermal stress but not from viral infection.

Using an anti-sense RNA approach, a mouse cell line containing dramatically reduced levels of the 90-kDa heat shock protein (hsp90) has been isolated. This line shows reduced growth at mildly elevated temperatures and reduced survival at highly elevated temperatures but is no more sensitive to herpes simplex virus infection than the parental cells. This is the first direct evidence of a role for an individual mammalian hsp in thermotolerance and suggests that individual hsps may be of different value in the response to various types of stress.

Animals↗
PubMed1991

The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable sensory neurons.

Transcription of herpes simplex virus (HSV) immediate-early (IE) genes does not occur in sensory neurons latently infected with the virus or following infection of neuronal cell lines. In neuronal cell lines this inability results from the weak activity of the viral IE promoters, which is caused by a neuron-specific repressor factor that binds specifically to the TAATGARAT motif in these promoters and to related octamer elements. Cells expressing this repressor contain an additional octamer-binding protein that is absent from permissive cells. We identify this factor as the lymphocyte- and neuron-specific octamer-binding protein Oct-2 and show that Oct-2 mRNA is also present in dorsal root ganglion neurons, the natural site of HSV latency in vivo. Moreover, artificially elevated expression of Oct-2 can repress the IE promoter. The potential role of Oct-2 in the initiation and maintenance of in vivo latent infection with HSV is discussed.

Animals↗
PubMed1991

Activation of endogenous retroviral transcription in SV40-transformed mouse cells.

We have previously isolated a number of cDNA clones that correspond to mRNAs present at higher levels in SV40-transformed cells than in the untransformed parental cells (Scott, M.R.D., Westphal, K.-H. and Rigby, P.W.J. (1983) Cell 34, 557-567). We have now determined the nucleotide sequence of the archetypal Set 2 clone, pAG59, and can thus identify it as corresponding to the env gene of the endogenous, ecotropic C-type retrovirus of Balb/c mice, Emv-1. We have shown that in the subset of SV40-transformed cells that express the provirus both of the proteins encoded by env, gp70 and p15E, are synthesised and that the former is displayed on the cell surface. We discuss the significance of these observations for the biology of SV40 transformation.

Animals↗
PubMed1991

A recombinant HIV provirus is synergistically activated by the HIV Tat protein and the HSV IE1 protein but not by the HSV IE3 protein.

To study the effects of regulatory proteins encoded by herpes viruses on the HIV long terminal repeat (LTR) in the presence or absence of HIV-encoded regulatory products, we prepared a proviral construct containing 5' and 3' HIV LTR, but lacking the coding sequences of any HIV proteins. This construct allowed the effects of herpesvirus regulatory proteins on the HIV LTR to be assessed in a construct similar to the HIV provirus whilst also allowing their interactions with HIV-encoded regulatory proteins to be studied. In this system, the herpes simplex virus (HSV) protein IE1 (ICPO) but not the IE3 (ICP4) protein can activate the HIV LTR, whereas both proteins are active on a single plasmid-borne HIV LTR. Although the activation of the LTR by IE1 is strongly stimulated by the HIV Tat protein, it can also be observed in the absence of Tat, indicating that HSV infection via IE1 has the potential to activate an entirely silent, latent HIV provirus.

Animals↗
PubMed1991

The B-cell and neuronal forms of the octamer-binding protein Oct-2 differ in DNA-binding specificity and functional activity.

B lymphocytes contain an octamer-binding transcription factor, Oct-2, that is absent in most other cell types and plays a critical role in the B-cell-specific transcription of the immunoglobulin genes. A neuronal form of this protein has also been detected in brain and neuronal cell lines by using a DNA mobility shift assay, and an Oct-2 mRNA is observed in these cells by Northern (RNA) blotting and in situ hybridization. We show that the neuronal form of Oct-2 differs from that found in B cells with respect to both DNA-binding specificity and functional activity. In particular, whereas the B-cell protein activates octamer-containing promoters, the neuronal protein inhibits octamer-mediated gene expression. The possible role of the neuronal form of Oct-2 in the regulation of neuronal gene expression and its relationship to B-cell Oct-2 are discussed.

Amino Acid Sequence↗
PubMed1991

Heat shock proteins and human disease.

At first sight it appears unlikely that a phenomenon which was first observed in 1962 as the appearance of specific puffs in the salivary gland chromosomes of the larvae of the fruit fly Drosophila busckii following exposure to elevated temperature [1] should, nearly 30 years later, attract considerable attention from clinicians and scientists interested in such diverse phenomena as autoimmune diabetes and myocardial infarction [2, 3]. The aim of this review is to discuss the information which has been accumulated about the heat shock proteins in the 30 years since their discovery and to indicate how this information has led to studies on their possible role in human disease.

Animals↗
PubMed1990

Regulation of herpes simplex virus immediate-early gene promoters in mouse neuroblastoma cells.

The non-permissivity of C1300 mouse neuroblastoma cells for herpes simplex virus (HSV) infection is due to a failure of such cells to transcribe the immediate-early (IE) genes following viral infection. We have transfected both C1300 cells and permissive cells with constructs in which each of the 5 IE promoters drives expression of the readily assayable chloramphenicol acetyl transferase (CAT) gene. These experiments show that the lack of IE gene transcription in C1300 cells is due to the weak activity of the five IE promoters in these cells compared to that observed in a range of permissive cell types. This effect is mediated both by up-stream elements and by sequences present in the minimal promoter. The different effects of DNA concentration on the activities of the minimal and complete promoters suggests that the up-stream sequences act by binding a repressor factor present in C1300 cells whilst the weak activity of the minimal promoter results from the absence of a positive factor in such cells.

Animals↗
PubMed1990

The herpes simplex virus protein Vmw65 can trans-activate both viral and cellular promoters in neuronal cells.

Transcription of the herpes simplex virus (HSV) immediate-early (IE) genes in lytic infection is dependent upon the formation of a complex between the cellular transcription factor Oct-1 and the HSV virion protein Vmw65. This complex then binds to the TAATGARAT sequence in the IE promoters and trans-activates the IE genes. Following infection of neuronal cells such as the C1300 neuroblastoma cell line, however, the viral (IE) genes are not transcribed and the lytic cycle is aborted at an early stage. We show here that the cellular factors necessary to form a trans-activating complex with Vmw65 are present in C1300 cells and that trans-activation of both viral and cellular promoters by Vmw65 can be observed in these cells. In contrast with permissive cells, however, trans-activation is only observed in C1300 cells at a high concentration of the target viral promoter and not at a low concentration of the target promoter, regardless of the amount of Vmw65 transfected. The significance of these effects for the regulation of latent infection and cellular gene expression in neuronal cells is discussed.

Animals↗
PubMed1990

Novel cell lines display properties of nociceptive sensory neurons.

Hybrid cell lines derived from neonatal rat dorsal root ganglia neurons fused with the mouse neuroblastoma N18Tg2 exhibit sensory neuron-like properties not displayed by the parental neuroblastoma. These properties include an inward (depolarizing) current with a conductance increase in response to activation of a bradykinin receptor, an inward (depolarizing) current with a conductance increase in response to the sensory excitotoxin capsaicin, the expression of sensory neuropeptides (substance P, CGRP and somatostatin), the expression of phosphatidylinositol-anchored molecules including adhesion molecules of the immunoglobulin superfamily that can be regulated in serum-free culture by nerve growth factor (N-CAM, F-3 and Thy-1), and low permissivity to herpes simplex virus infection. These lines thus provide appropriate models for the study of mechanisms involved in nociceptor activation and the regulation of expression of sensory-neuron specific markers including neuropeptides.

Animals↗
PubMed1990

Oestrogen enhances the responsiveness of the MMTV-LTR to glucocorticoid in ZR-75-1 human breast cancer cells.

Treatment of ZR-75-1 human breast cancer cells with oestrogen has no direct effect on the expression of a transfected MMTV-LTR but enhances its inducibility in response to glucocorticoid treatment. This effect which can be produced with both oestradiol and diethylstilbestrol is specific to induction of the MMTV-LTR, no effect of the treatment on expression driven by the RSV-LTR being observed. The effect can be observed in cells pre-treated with oestrogen prior to removal of DNA and glucocorticoid addition but not in cells where oestrogen is added after removal of the DNA. The possible mechanisms of these effects and their relationship to the induction of oestrogen-responsive genes by this hormone are discussed.

Breast Neoplasms↗