Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Co-transfection of HeLa cells with plasmids carrying human immunodeficiency virus (HIV) control elements along with plasmids harboring human retinoblastoma (RB) gene, results in the repression of transactivation of genes linked to HIV elements. Cells transfected with HIV LTR-linked chloramphenicol acetyl transferase (CAT) and TAT genes showed a dose-dependent decrease in CAT activity when increasing amounts of RB genes were transfected along with HIV genes. CAT mRNAs were not detected in HeLa cells transfected with HIV LTR CAT gene alone. Upon cotransfection of these cells with pTAT gene, large quantities of CAT messengers were observed. The TAT gene mediated expression of CAT gene was inhibited when cells were co-transfected with RB gene. These studies suggest that the RB gene represses HIV LTR directed CAT gene expression by interfering with the expression of HIV TAT gene.
Biochem Mol Biol Int 1993 Jan
PMID:Retinoblastoma gene inhibits transactivation of HIV-LTR linked gene expression upon co-transfection in He La cells. 849 May 68

Human PDH complex deficiency is an extremely heterogeneous disease in its presentation and clinical course. In an investigation at the level of the gene into ten cases of PDH complex (E1) deficiency, we found that all had mutations in the coding sequence of the X-linked E1 alpha gene while the E1 beta coding sequence was normal. Six of these patients (three males, three females) had missense mutations resulting in a changed amino acid residue in the E1 alpha subunit at positions amino acid 148 (in two siblings), 170, 202, 234 and 263 of the mature protein. Two of the females had one normal E1 alpha gene and one with a deletion at the sites of tandem repeats of AGTAAGA and TAT respectively. The two remaining females also had one normal E1 alpha gene and one with an insertion. Both insertions, one of 2 bp and one of 4 bp, occurred in DNA hotspots normally associated with deletions. Only two of these ten mutations have been reported in other patients previously. In the five cases (including the two siblings) where parent DNA was available, only in one case could the same mutation be found in the patient as well as the maternal genomic DNA.
Hum Mol Genet 1993 Apr
PMID:Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. 850 6

A point mutation in the plastome-encoded psaB gene of the mutant en:alba-1 of Antirrhinum majus L. was identified by an analysis of chloroplast DNA with a modified PCR-SSCP technique. Application of this technique is indicated when a gene or a group of genes is known in which the point mutation is located. Analysis of primary photosynthetic reactions in the yellowish white plastome mutant indicated a dysfunction of photosystem (PS) I. The peak wavelength of PS I-dependent chlorophyll (Chl) fluorescence emission at 77 K was shifted by 4 nm to 730 nm, as compared to fluorescence from wild-type. There were no redox transients of the reaction center Chl P700 upon illumination of leaves with continuous far-red light or with rate-saturating flashes of white light. The PS I reaction center proteins PsaA and PsaB are not detectable by SDS-PAGE in mutant plastids. Hence, plastome encoded PS I genes were regarded as putative sites of mutation. In order to identify plastome mutations we developed a modified SSCP (single-strand conformation polymorphism) procedure using a large PCR fragment which can be cleaved with various restriction enzymes. When DNA from wild-type and en:alba-1 was submitted to SSCP analysis, a single stranded HinfI fragment of a PCR product of the psaB gene showed differences in electrophoretic mobility. Sequence analysis revealed that the observed SSCP was caused by a single base substitution at codon 136 (TAT-->TAG) of the psaB gene. The point mutation produces a new stop codon that leads to a truncated PsaB protein. The results presented indicate that the mutation prevents the assembly of a functional PS I complex. The applicability to other plastome mutants of the new method for detection of point mutations is discussed.
Mol Gen Genet 1995 Dec 15
PMID:Detection of point mutations in chloroplast genes of Antirrhinum majus L. I. Identification of a point mutation in the psaB gene of a photosystem I plastome mutant. 854 19

Screening of a hybrid Barbus barbus-B. meridionalis genome was performed for CA, GA, TAT, TCT, TAG, TGT, TATT, TACT, ATCT motifs, and simultaneously on another fish species, tilapia S. melanotheron. Sequences of positive clones were obtained for Barbus and revealed that repetitive structure significantly depends on the motif: most TAT and TATT repeats contain small numbers of repeats, and these repeats are highly heterogeneous, whereas other motifs (we mainly obtained CA and GATA repeats) form longer and much more homogeneous arrays. Polymorphism data from five loci in two different species of barbel show that perfectly repetitive loci are much more variable than imperfect loci (TAT and TATT). We compared the frequency of positive clones for different repeat motifs between barbel and tilapia. For dinucleotide repeats (CA and GA), the comparison was extended to additional fish species, trout and sea bass, which were screened in nearly identical conditions for these motifs. The most salient feature of these comparisons reveals that arrays of dinucleotide motifs are significantly under-represented and shorter in Barbus than in other fish species. We propose an explanation that can account for most features of microsatellites characterizing the genome of barbel. A bias toward deletion affecting slipped-strand mispairing events would lead to shortening and loss of microsatellite loci. Such a bias would represent an efficient way of eliminating useless DNA from polyploidized species with an excessive amount of DNA.
Mol Ecol 1997 Feb
PMID:Does polyploidy lead to fewer and shorter microsatellites in Barbus (Teleostei:Cyprinidae)? 906 42

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22, changed codon 874 in the ligand-binding domain (exon H) from CAT for histidine to TAT for tyrosine and abolished a restriction site for the endonuclease SfaNI. SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant. CWR22, an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia. AR protein is present in cell nuclei by immunostaining as in other androgen-responsive tissues. Transcriptional activity of recombinant H874Y transiently expressed in CV1 cells in the presence of testosterone or dihydrotestosterone was similar to that of wild type AR. With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type AR induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant. H874Y, like the LNCaP cell mutant, was more responsive to estradiol and progesterone than was wild type AR. The antiandrogen hydroxyflutamide (10 nM) had greater agonist activity (4- to 7-fold) with both mutant ARs than with wild type AR. AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.
Mol Endocrinol 1997 Apr
PMID:Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. 909 97

p55Cdc is a mammalian homologue of a family of cell cycle proteins from widely divergent species, which contains WD repeats and has been implicated in cell cycle-regulated ubiquitin-mediated proteolysis. p55Cdc is highly expressed in proliferating but not in differentiated or growth-arrested cells. The expression, phosphorylation, and degradation of this protein have been shown to be cell cycle-regulated. We analyzed a 5.3-kb genomic region that contains the entire rat p55Cdc gene. The gene contains 10 exons ranging in size from 97 to 373 bp. The promoter region has a TAT box, four E-box consensus sequences, and potential binding sites for cell cycle-specific transcription factors. In transient transfection assays, a construct containing a 1000-nucleotide p55Cdc promoter region upstream of the chloramphenicol acetyltransferase reporter gene demonstrated a 12-fold increase in transcriptional activity. Finally, using radiation hybrid mapping techniques, we localized this gene to the human chromosome, 9q13-21.
Mol Genet Metab 1998 May
PMID:Genomic organization, 5' flanking enhancer region, and chromosomal assignment of the cell cycle gene, p55Cdc. 968 18

Recent studies have indicated that two elements in addition to the glucocorticoid response element (GRE) are involved in the induction of the endogenous TAT gene in FuS-5 rat hepatoma cells. The first is the 21 bp glucocorticoid modulatory element (GME) at -3648 bp, which causes reporter constructs to display both a left shift in the dose-response curve for glucocorticoids and increased percentages of agonist activity for antiglucocorticoids. The second is a negative element at -3340 to -3050 that blocks the action of the GME. This last observation raised the question of how GME activity can be expressed in Fu5-5 cells in the intact TAT gene that contains both the GME and the negative element. The present study identifies a third element, a "neutralizing" sequence, that restores the activity of the GME even when otherwise inactivated by the negative element. This neutralizing sequence was located within the region surrounding the GREs of the TAT gene but is separate from the GREs. The activity of the individual GME and negative elements was found to depend upon spacing. However, in combination with the natural GRE, the native TAT gene spacing of the GME and negative elements was able to reproduce the activity of the intact gene. Thus, a total of three additional elements (an activator, a negative element, and a neutralizer) appear to cooperate with the GREs in glucocorticoid induction of the TAT gene in Fu5-5 cells. While such a grouping of elements may be novel among steroid regulated genes, it is a not uncommon occurrence for the transcriptional control of other genes.
J Steroid Biochem Mol Biol 1998 Aug
PMID:Modulation of TAT gene induction by glucocorticoids involves a neutralizing sequence. 971 42

The natural steroid 11beta-hydroxyprogesterone is not only a modulator of 11beta-hydroxy-steroid dehydrogenase activity, but also an efficient inducer of tyrosine aminotransferase activity in hepatocytes. In contrast with the low affinity for the mineralocorticoid receptor. 11beta-hydroxyprogesterone binds well to both the glucocorticoid receptor and the carrier protein transcortin. It is accepted that the introduction of a 1:ene double bond into 3-keto 4:ene steroids increases the glucocorticoid potency, so that 3-keto-1,4:diene steroids show improved chemical stability and are more potent glucocorticoids than their respective 4:ene analogs. The steroid pregna-1,4-diene-11beta-ol-3,20-dione (deltaHOP) had previously been described as an anti-inflamatory compound and an inhibitor of macromolecular biosynthesis in thymocytes and lymphocytes. In such studies, deltaHOP also exhibited some particular glucocorticoid properties which made it attractive as a tool for the study of the mechanism of action of glucocorticoids. In the present paper we show that deltaHOP possesses some classical biological actions of glucocorticoids such as deposition of glycogen in rat liver, induction of TAT activity in hepatocytes, and inhibition of the uptake of leucine and thymidine by thymocytes. It also exhibits minimal sodium-retaining properties. Consistent with these biological effects, deltaHOP shows a 70 times lower relative binding affinity for the mineralocortioid receptor than aldosterone, but a reasonable affinity for the glucocorticoid receptor, and is as efficient as dexamethasone in dissociating the 90 kDa heat shock protein from the glucocorticoid receptor heterocomplex. However, the inhibition of the uptake of amino acids and nucleotides observed in the presence of deltaHOP is not efficiently blocked when thymocytes are coincubated in the presence of steroids with known antiglucocorticoid activity. deltaHOP is similarly inefficient in inducing chloramphenicol-acetyl transferase activity in cells transfected with a plasmid that possesses two canonical glucocorticoid-responsive elements. Unlike most glucocorticoids, deltaHOP does not induce the fragmentation of DNA in a regular pattern characteristic of apoptosis and it does not reduce thymus weight. This unusual dissociation of glucocorticoid parameters makes deltaHOP a useful tool to discriminate between mechanisms of action by which steroids can exert their biological effects.
Mol Cell Endocrinol 1999 Mar 25
PMID:The glucocorticoid properties of the synthetic steroid pregna-1,4-diene-11beta-ol-3,20-dione (deltaHOP) are not entirely correlated with the steroid binding to the glucocorticoid receptor. 1037 32

Diversity in the tRNALEU1 intron of the chloroplast genome of Spartina was used to study hybridization of native California cordgrass, Spartina foliosa, with S. alterniflora, introduced to San Francisco Bay approximately 25 years ago. We sequenced 544 bases of the tRNALEU1 intron and found three polymorphic sites, a pyrimidine transition at site 126 and transversions at sites 382 and 430. Spartina from outside of San Francisco Bay, where hybridization between these species is impossible, gave cpDNA genotypes of the parental species. S. foliosa had a single chloroplast haplotype, CCT, and this was unique to California cordgrass. S. alterniflora from the native range along the Atlantic coast of North America had three chloroplast haplotypes, CAT, TAA, and TAT. Hybrids were discriminated by random amplified polymorphic DNA (RAPD) phenotypes developed in a previous study. We found one hybrid that contained a cpDNA haplotype unknown in either parental species (TCT). The most significant finding was that hybridization proceeds in both directions, assuming maternal inheritance of cpDNA; 26 of the 36 hybrid Spartina plants from San Francisco Bay contained the S. foliosa haplotype, nine contained haplotypes of the invading S. alterniflora, and one had the cpDNA of unknown origin. Furthermore, cpDNA of both parental species was distributed throughout the broad range of RAPD phenotypes, suggesting ongoing contributions to the hybrid swarm from both. The preponderance of S. foliosa cpDNA has entered the hybrid swarm indirectly, we propose, from F1s that backcross to S. foliosa. Flowering of the native precedes by several weeks that of the invading species, with little overlap between the two. Thus, F1 hybrids would be rare and sired by the last S. foliosa pollen upon the first S. alterniflora stigmas. The native species produces little pollen and this has low viability. An intermediate flowering time of hybrids as well as pollen that is more vigourous and abundant than that of the native species would predispose F1s to high fitness in a vast sea of native ovules. Thus, spread of hybrids to other S. foliosa marshes could be an even greater threat to the native species than introductions of alien S. alterniflora.
Mol Ecol 2000 Jun
PMID:Reciprocal hybrid formation of Spartina in San Francisco Bay. 1084 92

Although mouse models have been increasingly used for studies of cardiac pathophysiology, there is little information regarding cultured murine cardiac myocytes. Accordingly, we have developed a cell culture model of neonatal mouse cardiac myocytes by modifying a protocol used to prepare neonatal rat myocytes. The principal change is the substitution of cytosine arabinoside for bromodeoxyuridine to prevent fibroblast proliferation. Neonatal murine myocytes exhibited persistent spontaneous contraction and were viable for up to 14 days in culture. By flow cytometry 85% of the cells were cardiac myocytes. In sparse cultures (average cell density 259 cells/mm(2)), both hypoxic preconditioning (n=5) and phenylephrine pretreatment (n=8) produced significant protection of cardiac myocytes from cell death during a prolonged period of severe hypoxia (<0.5% O(2)for 18-20 h, both P<0.05). The phenylephrine effect was inhibited by the alpha(1)-adrenoceptor antagonist prazosin (n=4, P<0.05) and by an xi PKC peptide antagonist (xi V1-2) coupled to a TAT peptide (n=5, P<0. 05). Interestingly, the mixed alpha(1)- and beta -adrenoceptor agonist norepinephrine, which stimulates hypertrophy as measured by(14)[C]phenylalanine incorporation in neonatal rat cardiac myocytes, did not cause hypertrophy in mouse myocytes, suggesting that the signaling pathways for myocardial protection and hypertrophy are likely to be both divergent and species specific. In cardiac myocytes prepared from transgenic mice either homozygous or heterozygous for human Cu/Zn superoxide dismutase, there was protection from cell death (n=3) and restoration of(14)[C]phenyl- alanine uptake (n=4) during prolonged hypoxia (1% O(2)for 3 days, both P<0.05). We conclude that this cellular model, which is relatively simple to prepare, can be used for in-vitro examination of cardiac protection induced by preconditioning agents, various transgenes, and potentially by targeted gene deletions.
J Mol Cell Cardiol 2000 Oct
PMID:Neonatal mouse cardiac myocytes exhibit cardioprotection induced by hypoxic and pharmacologic preconditioning and by transgenic overexpression of human Cu/Zn superoxide dismutase. 1101 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>