Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Infection of potato leaves (Solanum tuberosum L. cv. Datura) by the late blight fungus Phytophthora infestans, or treatment with fungal elicitor leads to a strong increase in chitinase and 1,3-beta-glucanase activities. Both enzymes have been implicated in the plant's defence against potential pathogens. In an effort to characterize the corresponding genes, we isolated complementary DNAs encoding the basic forms (class I) of both chitinase and 1,3-beta-glucanase, which are the most abundant isoforms in infected leaves. Sequence analysis revealed that at least four genes each are expressed in elicitor-treated leaves. The structural features of the potato chitinases include a hydrophobic signal peptide at the N-terminus, a hevein domain which is characteristic of class I chitinases, a proline- and glycine-rich linker region which varies among all potato chitinases, a catalytic domain, and a C-terminal extension. The potato 1,3-beta-glucanases also contain a N-terminal hydrophobic signal peptide and a C-terminal extension, the latter comprising a potential glycosylation site. RNA blot hybridization experiments showed that basic chitinase and 1,3-beta-glucanase are strongly and coordinately induced in leaves in response to infection, elicitor treatment, ethylene treatment, or wounding. In addition to their activation by stress, both types of genes are regulated by endogenous factors in a developmental and organ-specific manner. Appreciable amounts of chitinase and 1,3-beta-glucanase mRNAs were found in old leaves, stems, and roots, as well as in sepals of healthy, untreated plants, whereas tubers, root tips, and all other flower organs (petals, stamen, carpels) contained very low levels of both mRNAs. In young leaves and stems, chitinase and 1,3-beta-glucanase were differentially expressed. While chitinase mRNA was abundant in these parts of the plant, 1,3-beta-glucanase mRNA was absent. DNA blot analysis indicated that in potato, chitinase and 1,3-beta-glucanase are encoded by gene families of considerable complexity.
Plant Mol Biol 1994 Jan
PMID:Primary structure and expression of mRNAs encoding basic chitinase and 1,3-beta-glucanase in potato. 811 Oct 37

The p53 tumor suppressor protein, which is commonly mutated in human cancers, has been shown to interact directly with virally encoded from papillomavirus, adenovirus, and simian virus 40. The disruption of p53 function may be required for efficient replication of certain viruses and may also play a role in the development of virally induced malignancies. Infection with Epstein-Barr virus (EBV) has been associated with the development of B-cell lymphomas and nasopharyngeal carcinoma. Here we show that the EBV immediate-early protein, BZLF1 (Z), which is responsible for initiating the switch from latent to lytic infection, can interact directly in vitro and in vivo with the tumor suppressor protein, p53. This interaction requires the coiled-coil dimerization domain of the Z protein and the carboxy-terminal portion of p53. Overexpression of wild-type p53 inhibits the ability of Z to disrupt viral latency. Likewise, Z inhibits p53-dependent transactivation in lymphoid cells. The direct interaction between Z and p53 may play a role in regulating the switch from latent to lytic viral infection.
Mol Cell Biol 1994 Mar
PMID:Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency. 811 24

Cytomegalovirus (CMV) is a member of the herpes virus group. Infection results in a variety of disorders which depend largely on the immune status of the host. A well known property of CMV is that after primary infection the virus persists in the body of the host resulting in latency. Severe immunodepression or immunodeficiency can cause reactivation of the virus from its latent state, leading to endogenous reinfection. In contrast to other herpes viruses, such as herpes simplex virus which persists in neurons, and Epstein Barr virus which persists in B lymphocytes, little is known about the localization of latent CMV. In order to obtain more insight in the organ or cell type serving as a reservoir for latent CMV, it is important to know more about the course of natural infection and the cells and organs involved. When more information is available about the localization of latent virus, studies concerning the physical state of viral DNA or the extent of viral transcription and/or translation will follow in the near future. In this review some properties of the epidemiology and transmission of human CMV, as well as data about acute infection will be given. In addition, some characteristics of the localization of latent CMV and the physical state of the virus will be discussed. Where necessary, particularly regarding insight into CMV-host interactions, knowledge of animal, particularly murine, rat and guinea pig CMV infections, will be discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Cytomegalovirus and latency: an overview. 814 53

Expression of the beta-casein milk protein gene in the mammary epithelial cell line HC11 is primarily regulated at the transcriptional level. A 338-bp segment of promoter sequence 5' of the transcription start site is sufficient to confer inducibility by the lactogenic hormones insulin, glucocorticoid hormone, and prolactin. Positively and negatively acting promoter elements and specific DNA binding proteins have been identified. The binding of the mammary gland factor MGF to a site between -80 and -100 is indispensable for hormonal induction of transcription. Binding of MGF activity to DNA is greatly enhanced by the action of the lactogenic hormones. Repression of transcription in the uninduced state is mediated by a promoter element located adjacent to the MGF binding site at positions -110 to -150. This repressor element consists of two interacting protein binding sites. A nuclear factor that binds specifically to the proximal site between positions -110 and -120 has been characterized and found to be identical with the nuclear factor YY1 (delta, NF-E1). YY1 does not bind to the distal site. The simultaneous mutation in the proximal and the distal sites results in high, hormone-independent transcription. This finding suggests that YY1 plays a functional role in the repression and acts in conjunction with a second DNA binding protein. Comparison of YY1 DNA binding activity in uninduced and hormone-induced cells showed that relief of repression is not mediated by changes in the concentration or binding affinity of YY1. Infection of HC11 cells with a YY1-expressing recombinant retrovirus resulted in overexpression of YY1 but did not suppress hormonal induction. The addition of purified MGF decreased YY1 binding to its DNA recognition site in vitro. This finding indicates that MGF regulates the DNA binding activity of YY1 and thereby may cause the relief of transcriptional repression.
Mol Cell Biol 1994 Jan
PMID:The nuclear factor YY1 participates in repression of the beta-casein gene promoter in mammary epithelial cells and is counteracted by mammary gland factor during lactogenic hormone induction. 826 81

Infection of PC12 cells with Japanese encephalitis (JE) virus caused marked proliferation of the protein secretory system. Accordingly, in this study the morphogenesis of the secretory organelles, i.e., rough endoplasmic reticulum (RER) and the Golgi apparatus, in JE virus-infected PC12 cells was analyzed by electron microscopical observation. Starting 24 h postinoculation (p.i.), a structure that represented nascent RER appeared in the cytoplasm in the form of rows of ribosomes which surrounded membrane-unbounded, electron-lucent lacunae in a reticular, honey-comb pattern (reticular RER). Although the reticular RER lacked membrane components, its lacunae contained progeny virions, indicating that the rows of ribosomes synthesized the viral proteins and discharged them into the lacunae for the viral assembly. The reticular RER apparently transformed into the familiar lamellar RER during the RER morphogenesis as the lacunae coalesced to form flat cisternae and RER membrane assembled to border the cisternae. These findings indicated that the proliferating RER was the site of not only active protein synthesis but also active membrane biogenesis. The proliferating RER released a large number of membrane vesicles including virion-carrying vesicles into the cytoplasm. These vesicles congregated in the juxtanuclear region, especially around the centrioles, and fused to existing Golgi complexes for enlargement or fused among themselves to form new Golgi complexes. The present study, therefore, indicated that (a) nascent RER was formed by polysomes that arranged themselves in rows of ribosomes without participation of a preexisting membrane framework of endoplasmic reticulum (ER), (b) membrane components of RER were assembled de novo within the structure during the RER morphogenesis, and (c) RER released membrane vesicles that moved to the Golgi apparatus and contributed to the morphogenesis of the Golgi apparatus. Possible causative mechanisms involved in the proliferation of the secretory system in JE virus-infected PC12 cells are discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Morphogenesis of the protein secretory system in PC12 cells infected with Japanese encephalitis virus. 828 19

In an effort to correlate biochemical characteristics of the beta-adrenergic receptor complex with myocardial function, mouse myocardial GTP-binding proteins, specifically substrates for pertussis toxin (PT), were analysed with regard to the influence of infection with Trypanosoma cruzi, the causative agent of Chagas' cardiomyopathy. Infection was found to decrease in a non-uniform manner the magnitude of ADP-ribosylation in the PT substrates. High detergent concentrations attenuated the infection-associated decrease in PT-dependent ADP-ribosylation. Infection also altered the kinetics of the PT-dependent ADP-ribosylation reaction from a time course wherein maximal PT-dependent ADP-ribosylation occurred after 12 h incubation in control animals to one in which maximal PT-dependent ADP-ribosylation occurred after 3 h incubation and thereafter declined. Immunochemical analysis of the PT-substrates revealed an infection-associated decrease in alpha i1, alpha o, an increase in alpha i2 and no change in alpha i3. Verapamil treatment, which prevents the clinical consequences of infection, did not influence any of the infection-associated changes in PT-dependent ADP-ribosylation of GTP-binding protein substrates or their immunochemical properties. Complementary studies using isolated rat neonatal cardiocytes infected with the parasite further substantiated the finding that the infection-associated decrease in PT-dependent ADP-ribosylation and the associated change in the kinetics of the reaction were properties uniquely associated with the presence of the parasite.
J Mol Cell Cardiol 1993 Nov
PMID:Evidence that myocardial pertussis toxin substrates are uniquely altered in acute murine Chagas' disease in a manner unrelated to myocardial dysfunction. 830 65

In vivo studies of Friend virus erythroleukemia have implied that proviral integrations adjacent to the gene for the Ets-related transcription factor PU.1 may inhibit the commitment of erythroblasts to differentiate and cause their capability for indefinite transplantation (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 62:4129-4135, 1988; R. Paul, S. Schuetze, S. L. Kozak, C. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test this hypothesis, we ligated PU.1 cDNA into a retroviral vector and studied its effects on cultured cells. Infection of fibroblasts with PU.1-encoding retrovirus resulted in PU.1 synthesis followed by nuclear pyknosis, cell rounding, and degeneration. In contrast, in long-term bone marrow cultures, erythroblasts were efficiently and rapidly immortalized. The resulting cell lines were polyclonal populations that contained PU.1, were morphologically blast-like, required erythropoietin and bone marrow stromal cells for survival and proliferation, and spontaneously differentiated at low frequency to synthesize hemoglobin. After 9 months in culture, erythroblasts became stroma independent, and they then grew as clonal cell lines. We conclude that PU.1 perturbs the pathway(s) that controls potential for indefinite proliferation and that it can be used to generate permanent erythroblast cell lines.
Mol Cell Biol 1993 Sep
PMID:The Ets-related transcription factor PU.1 immortalizes erythroblasts. 835 8

There have been numerous reports of altered drug clearance during episodes of viral infection and during the clinical use of recombinant interferons, but there have been very few reports regarding the effect of active bacterial infections on cytochrome P450-mediated metabolism. The objective of this study was to determine the mechanism by which the Gram-positive bacteria Listeria monocytogenes causes a depression of cytochrome P450-mediated biotransformation in mice. After induction with beta-napthoflavone, hepatic microsomal cytochrome P450 levels were reduced by 40% and ethoxyresorufin-O-dealkylase (EROD) activity was decreased by 65% in mice infected for 48 hr. The loss of EROD activity was accompanied by losses of cytochrome P450IA apoenzyme and cytochrome P450IA mRNA. Listeria infection did not affect total mRNA levels, as determined by oligo(dT)18 hybridization. The time course of these effects demonstrated that an up-regulation of cytochrome P450IA preceded the loss of this isozyme and that changes in cytochrome P450IA mRNA preceded the changes in apoenzyme levels and EROD activity. In hepatic microsomes from uninduced mice, cytochrome P450 levels and the rates of dealkylation of ethoxyresorufin, benzyloxyresorufin, pentoxyresorufin, and aminopyrine were significantly reduced, by 40-60%, after 48 hr of infection. The decrease in aminopyrine-N-demethylase activity was accompanied by a loss of cytochrome P450IID9 mRNA after 48 hr of infection. Cytochrome P450IID9 mRNA levels returned to normal after 96 hr of infection, whereas aminopyrine-N-demethylase activity was still decreased at this time. No up-regulation of cytochrome P450IID9 occured before the loss of this isozyme. The results of this study indicate that the changes in the levels of cytochrome P450IA and cytochrome P450IID9 that are observed during L. monocytogenes infection occur at a pretranslational step. If other bacteria have a similar capacity to depress cytochrome P450 by such a mechanism, then drugs with narrow therapeutic indices should be administered with caution during infectious diseases caused by bacteria or viruses.
Mol Pharmacol 1993 Apr
PMID:Mechanism of hepatic cytochrome P450 modulation during Listeria monocytogenes infection in mice. 837 89

Infection of cells with adenovirus or transfection of cells with double-stranded RNA (dsRNA) activates transcription of the alpha/beta interferon-stimulated genes (ISGs). Induction of ISG expression by adenovirus appears to be mediated through the same DNA target that is responsive to alpha/beta interferons, the interferon-stimulated response element (ISRE). Transcriptional induction by alpha/beta interferons has been shown previously to be mediated by the activation of a latent cytoplasmic transcription factor, ISGF3, that translocates to the nucleus and binds to the ISRE. However, ISG expression induced by adenovirus or dsRNA appears to be mediated by unique dsRNA-activated factors (DRAFs) that bind to the ISRE. The activation of these preexisting factors by dsRNA does not require new protein synthesis. Two DRAFs, DRAF1 and DRAF2, have been identified in our studies as ISRE-binding complexes in gel mobility shift assays. The ISRE-binding specificity of DRAF1 is similar to that of ISGF3; however, the ISRE-binding specificity of DRAF2 is distinct. Activation of DRAF1 and DRAF2 is independent of interferon action since it occurs in cells that are nonresponsive to interferon and in cells that lack the alpha/beta interferon locus. The activation pathway of DRAF1 and DRAF2 is blocked by the protein kinase inhibitors staurosporine and genistein. This is analogous to the interferon signal transduction pathway and suggests that phosphorylation, possibly tyrosine phosphorylation, is involved in activation of these factors.
Mol Cell Biol 1993 Jun
PMID:Double-stranded RNA activates novel factors that bind to the interferon-stimulated response element. 838 46

Infection with adenovirus type 12 (Ad12) induces four fragile sites in the human genome (H.F. Stich, G.L. van Hoosier, and J.J. Trentin, Exp. Cell Res. 34:400-403, 1964; H. zur Hausen, J. Virol. 1:1174-1185, 1967). The major site, at 17q21-22, contains the U2 gene cluster, which is specifically disrupted by infection in at least a percentage of the cells (D.M. Durnam, J.C. Menninger, S.H. Chandler, P.P. Smith, and J.K. McDougall, Mol. Cell. Biol. 8:1863-1867, 1988). For direct assessment of whether the U2 locus is the target of the Ad12 effect, an artificial locus, constructed in vitro and consisting of tandem arrays of the U2 6-kbp monomer, was transfected into human cells. We report that integration of this artificial locus on the p arm of chromosome 13 creates a new Ad12-inducible fragile site.
Mol Cell Biol 1993 Oct
PMID:Generation of a new adenovirus type 12-inducible fragile site by insertion of an artificial U2 locus in the human genome. 841 8


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