Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Oncostatin M belongs to the subfamily of hematopoietin cytokines that binds a receptor complex containing gp130. To date, only the human form of oncostatin M has been identified, and its evolutionary conservation is unresolved. We have isolated a bovine gene whose open reading frame encodes a precursor protein that is 58% identical to human oncostatin M. A comparison of the bovine and human amino acid sequences predicts significant similarity, including the four-alpha-helical-bundle structure and the placement of disulfide bridges. As with the human protein, bovine oncostatin M binds specific receptors on human H2981 cells and inhibits the proliferation of human A375 tumor cells and mouse M1 leukemia cells. To identify activities regulated in vivo, we injected bovine oncostatin M fusion genes containing various tissue-specific promoters into mouse embryos. The frequencies of transgenic mice were reduced significantly, suggesting that overexpression of the bovine cytokine is detrimental to normal mouse development. In addition to deaths associated with expression in neurons and keratinized epithelia, bovine oncostatin M caused abnormalities in bone growth and spermatogenesis, stimulated fibrosis surrounding islets in the pancreas, and disrupted normal lymphoid tissue development. This work establishes the existence of a nonprimate oncostatin M gene and provides the first demonstration that this cytokine can function in a pleiotropic manner in vivo. Information regarding bovine oncostatin M may help characterize the structure and function of this cytokine in other vertebrate species.
Mol Cell Biol 1995 May
PMID:Developmental abnormalities in mice transgenic for bovine oncostatin M. 773 18

A Bombyx mori cDNA was cloned that hybridized with Hyalophora cecropia attacin probe and its nucleotide sequence was determined. This cDNA consisted of 846 nucleotides and the deduced amino acid sequence showed that the cDNA encodes an attacin precursor protein. The putative mature protein of B. mori attacin had 70.4, 68.3 and 18.8% identity in amino acid sequences with that of H. cecropia acidic and basic attacins and Sarcophaga peregrina sarcotoxin IIA, respectively. B. mori and H. cecropia attacins and S. peregrina sarcotoxin IIA had two subdomains in each G domain, suggesting that common amino acid residues in the subdomains are conserved during evolution and plays an important role in the activity of the antibacterial proteins. Expression of B. mori attacin gene was rapidly induced by the injection of Escherichia coli cells into B. mori larvae and continued at least for 48 h mainly in fat bodies and hemocytes.
Insect Biochem Mol Biol 1995 Mar
PMID:Characterization of a Bombyx mori cDNA encoding a novel member of the attacin family of insect antibacterial proteins. 777 56

17 beta-estradiol induces the synthesis of massive amounts of the hepatic mRNA encoding the Xenopus laevis egg yolk precursor protein, vitellogenin. Vitellogenin mRNA exhibits a half life of approx. 500 h when 17 beta-estradiol is present, and 16 h after removal of 17 beta-estradiol from the culture medium. We recently reported that Xenopus liver contains a protein, which is induced by 17 beta-estradiol and binds with a high degree of specificity to a binding site in a segment of the 3'-untranslated region (3'-UTR) of vitellogenin mRNA implicated in 17 beta-estradiol stabilization of vitellogenin mRNA. To determine if this mRNA binding protein was specific to this system, or if it was present elsewhere, and regulated by other steroids, we examined the tissue distribution and androgen regulation of this protein. Substantial amounts of the vitellogenin 3'-UTR binding protein were found in several Xenopus tissues including testis, ovary and muscle. In the absence of hormone treatment, lung and intestine contained minimal levels of the mRNA binding protein. Testosterone administration induced the vitellogenin 3'-UTR RNA binding protein in several tissues. Additionally, we found a homologous mRNA binding protein in MCF-7, human breast cancer cells. Although the MCF-7 cell protein was not induced by 17 beta-estradiol, the MCF-7 cell mRNA binding protein appears to be closely related to the Xenopus protein since: (i) the human and Xenopus proteins elicit gel shifted bands with the same electrophoretic mobility using the vitellogenin mRNA 3'-UTR binding site; (ii) The human and Xenopus proteins exhibit similar binding specificity for the vitellogenin 3'-UTR RNA binding site; and (iii) RNA from MCF-7 cells is at least as effective as RNA from control male Xenopus liver in blocking the binding of the Xenopus and human proteins to the vitellogenin mRNA 3'-UTR binding site. Its broad tissue distribution and regulation by both 17 beta-estradiol and testosterone suggests that this mRNA binding protein may play a significant role in steroid hormone regulation of mRNA metabolism in many vertebrate cells.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Tissue distribution, hormone regulation and evidence for a human homologue of the estrogen-inducible Xenopus laevis vitellogenin mRNA binding protein. 777 54

Expression of the gene encoding neurotensin/neuromedin N (NT/N) is mostly limited to the brain and specialized enteroendocrine cells (N cells) of the distal small intestine. We have analyzed the NT/N DNA sequences upstream of the RNA start site that direct cell-specific expression using a novel human endocrine cell line, BON, that resembles intestinal N cells in several important aspects, including NT/N precursor protein processing, ratios of different NT/N mRNA forms, and high levels of constitutive expression of the NT/N gene. Transient transfection assays with plasmids with progressive 5' deletions of the rat NT/N promoter identified the proximal 216 bp of 5' flanking sequences as essential for high-level constitutive NT/N expression in BON cells. In addition, a detailed mutational analysis defined multiple regions within the proximal 216 bp that contribute to cell-specific NT/N expression. These elements include a proximal cyclic AMP response element (CRE)/AP-1-like motif (TGACATCA) that binds c-Jun, JunD, CRE-binding (CREB), and ATF proteins, a near-consensus glucocorticoid response element, and a distal consensus AP-1 site that binds c-Fos, Fra-1, and JunD. In addition, elements contained within two 21-bp imperfect direct repeats play an important role in NT/N expression in BON cells and may bind novel factors that act as positive regulators of NT/N expression. DNase I footprinting and gel shift analyses demonstrate that the sites identified by mutational analysis, and at least one additional site, specifically bind BON cell nuclear proteins in vitro. We speculate that a complex pattern of regulation requiring interaction between a proximal CRE/AP-1-like motif and other upstream control elements play an important role in the high-level constitutive expression of NT/N in the human endocrine cell line BON. In addition, the BON cell line provides a unique model to further characterize the factors regulating cell-specific NT/N expression and to better understand the mechanisms responsible for the terminal differentiation of the N-cell lineage in the gut.
Mol Cell Biol 1995 Jul
PMID:Characterization of promoter elements required for cell-specific expression of the neurotensin/neuromedin N gene in a human endocrine cell line. 779 94

cDNA sequences encoding the 42 kDa glycoprotein elicitor from the oomycete, Phytophthora megasperma, that induces the defense response in parsley have been cloned and sequenced. The 5' end of the mRNA matches a consensus derived from sequences surrounding the transcription initiation sites of seven other oomycete genes. The major transcript of 1802 nucleotides contains a 529-codon open reading frame, which was predicted to encode a 57 kDa precursor protein. On the basis of peptide sequencing, the N-terminus of the mature protein is at position 163, suggesting that proteolytic processing events, in addition to signal peptide cleavage, generate the protein purified from the fungal culture filtrate. Expression studies in Escherichia coli with the cDNA as well as smaller subfragments demonstrated that a region of 47 amino acids located in the C-terminal third of the protein was sufficient to confer elicitor activity. The gene encoding the elicitor was found to be a member of a multigene family in P. megasperma. Homologous families of differing sizes were found in all eight other Phytophthora species tested, but not in other filamentous fungi including other Oomycetes. No significant similarity of the elicitor preprotein to sequences present in the databases has yet been detected.
Mol Gen Genet 1995 Jan 06
PMID:Molecular characterization of nucleotide sequences encoding the extracellular glycoprotein elicitor from Phytophthora megasperma. 782 12

The beta amyloid peptide which accumulates within the brains of patients with Alzheimer's disease (AD) is proteolytically derived from a precursor protein (beta PP). We established and characterized four stably transformed human neuroblastoma cell lines which conditionally expressed a partial beta PP fusion protein (amino-17 residues+carboxyl-99 residues; S beta C). Conditional expression of S beta C was achieved using a tetracycline-responsive promoter system. Expression of this fusion protein in one of the cell lines resulted in pronounced cytotoxicity. Addition of n6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate and/or fetal bovine serum to the culture medium of this cell line further elevated the level of S beta C expression and enhanced the associated cytotoxicity. Conditioned medium, acquired from cells expressing S beta C, was not cytotoxic. These findings suggest that modulation of beta PP expression and/or metabolism can have cytotoxic consequences. This is the first report of cytotoxic effects mediated by conditional expression of a beta PP derivative. This immortal cell line provides a unique opportunity to screen for complementary DNAs which suppress this toxicity. Such cDNAs could help elucidate the processes underlying S beta C mediated cytotoxicity which in turn could further our understanding of the pathogenesis of AD and could also provide additional candidate genes for various forms of familial AD.
Brain Res Mol Brain Res 1994 Oct
PMID:Cytotoxicity mediated by conditional expression of a carboxyl-terminal derivative of the beta-amyloid precursor protein. 785 49

Seven bovine follistatin (FS) cDNA clones were isolated from a bovine ovarian follicle cDNA library. The predicted amino acid sequences revealed that six of the cDNA clones represented an FS precursor of 344 amino acids which corresponded to a mature FS of 315 amino acids (FS 315), with one cDNA clone containing the entire coding sequence including 180 nucleotides of 5' untranslated sequence. The predicted amino acid sequence of the seventh cDNA clone, which differed in the 3' coding sequence, represented a precursor protein of 317 amino acids, corresponding to a mature FS of 288 amino acids (FS 288). This clone encoded an identical amino acid sequence to the other six cDNA clones except that the C terminal of FS 315 was truncated by 27 amino acids. The sequence of bovine FS was found to contain 36 cysteine residues and 2 potential N-linked glycosylation sites. The predicted amino acid sequence of bovine FS has overall sequence homologies of 98% with ovine FS and 97% with human FS.
J Mol Endocrinol 1994 Dec
PMID:Isolation and characterization of bovine follistatin cDNA. 789 50

The psbO gene of cyanobacteria, green algae and higher plants encodes the precursor of the 33 kDa manganese-stabilizing protein (MSP), a water-soluble subunit of photosystem II (PSII). Using a pET-T7 cloning/expression system, we have expressed in Escherichia coli a full-length cDNA clone of psbO from Arabidopsis thaliana. Upon induction, high levels of the precursor protein accumulated in cells grown with vigorous aeration. In cells grown under weak aeration, the mature protein accumulated upon induction. In cells grown with moderate aeration, the ratio of precursor to mature MSP decreased as the optical density at induction increased. Both forms of the protein accumulated as inclusion bodies from which the mature protein could be released under mildly denaturing conditions that did not release the precursor. Renatured Arabidopsis MSP was 87% as effective as isolated spinach MSP in restoring O2 evolution activity to MSP-depleted PSII membranes from spinach; however, the heterologous protein binds to spinach PSIIs with about half the affinity of the native protein. We also report a correction to the previously published DNA sequence of Arabidopsis psbO (Ko et al., Plant Mol Biol 14 (1990) 217-227).
Plant Mol Biol 1994 Oct
PMID:Reconstitution of the spinach oxygen-evolving complex with recombinant Arabidopsis manganese-stabilizing protein. 794 62

Polyphenol oxidase (PPO) was purified to homogeneity from Sultana grapes yielding a single protein with an apparent molecular mass of 40 kDa as determined by SDS-PAGE. A degenerate oligonucleotide primer based on the N-terminal amino acid sequence of this purified 40 kDa grape PPO protein was used to amplify a 1650 bp cDNA clone (GPO1M) by 3' rapid amplification of cDNA ends (3'-RACE). GPO1M hybridized to a single 2.2 kb transcript from grape berry mRNA indicating the presence of further upstream sequence which was cloned using 5'-RACE PCR. The complete 1990 bp cDNA (GPO1) encodes a 67 kDa protein consisting of a 10.6 kDa chloroplast transit peptide, a 40.5 kDa catalytic unit containing two copper-binding regions and a 16.2 kDa C-terminal extension. Southern analysis suggested the presence of only one PPO gene in grapevine. High levels of gene expression were found in young developing berries, leaves and roots, but there was little expression in mature tissues. Biogenesis of PPO in grapevine tissues, appears to involve synthesis of a 67 kDa precursor protein which is imported into the chloroplast and processed to remove a 10.6 kDa chloroplast transit peptide from the N-terminus and a 16.2 kDa peptide of unknown function from the C-terminus.
Plant Mol Biol 1994 Oct
PMID:Molecular cloning and characterisation of grape berry polyphenol oxidase. 794 97

The NF-kappa B1 subunit of the transcription factor NF-kappa B is derived by proteolytic cleavage from the N terminus of a 105-kDa precursor protein. The C terminus of p105NF-kappa B1, like those of I kappa B proteins, contains ankyrin-related repeats that inhibit DNA binding and nuclear localization of the precursor and confer I kappa B-like properties upon p105NF-kappa B1. Here we report the characterization of two novel NF-kappa B1 precursor isoforms, p84NF-kappa B1 and p98NF-kappa B1, that arise by alternate splicing within the C-terminal coding region of murine nfkb1. p98NF-kappa B1, which lacks the 111 C-terminal amino acids (aa) of p105NF-kappa B1, has a novel 35-aa C terminus encoded by an alternate reading frame of the gene. p84NF-kappa B1 lacks the C-terminal 190 aa of p105NF-kappa B1, including part of ankyrin repeat 7. RNA and protein analyses indicated that the expression of p84NF-kappa B1 and p98NF-kappa B1 is restricted to certain tissues and that the phorbol myristate acetate-mediated induction of p84NF-kappa B1 and p105NF-kappa B1 differs in a cell-type-specific manner. Both p84NF-kappa B1 and p98NF-kappa B1 are found in the nuclei of transfected cells. Transient transfection analysis revealed that p98NF-kappa B1, but not p105NF-kappa B1 or p84NF-kappa B1, acts as a transactivator of NF-kappa B-regulated gene expression and that this is dependent on sequences in the Rel homology domain required for DNA binding and on the novel 35 C-terminal aa of this isoform. In contrast to previous findings, which indicated that p105NF-kappa B1 does not bind DNA, all of the NF-kappa B1 precursors were found to specifically bind with low affinity to a highly restricted set of NF-kappa B sites in vitro, thereby raising the possibility that certain of the NF-kappa B1 precursor isoforms may directly modulate gene expression.
Mol Cell Biol 1994 Dec
PMID:Alternate RNA splicing of murine nfkb1 generates a nuclear isoform of the p50 precursor NF-kappa B1 that can function as a transactivator of NF-kappa B-regulated transcription. 796 79


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