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)

Rab escort proteins (REPs) bind to newly synthesized Rab proteins and remain bound during and after the attachment of a geranylgeranyl (GG) group by the catalytic component of the Rab GG transferase. Transfer of the GG group is absolutely dependent on the participation of a REP. REP-1, the first characterized REP, is produced by a gene on the X chromosome that is defective in patients with choroideremia, a form of retinal degeneration. Cremers et al. (Cremers, F.P.M., Molloy, C. M., van de Pol, D. J. R., van den Hurk, J. A. J. M., Bach, I., Geurts van Kessel, A. H. M., and Ropers, H.-H. (1992) Hum. Mol. Genet. 1, 71-75) isolated a related gene, designated choroideremia-like, which encodes a protein that closely resembles REP-1. In the current studies, we produced REP-1 and REP-2 by recombinant DNA methods and showed that both proteins were approximately equal in facilitating the attachment of GG groups to several Rab proteins, including Rab1A, Rab5A, and Rab6. However, REP-2 was only 25% as active as REP-1 in supporting GG attachment to Rab3A and Rab3D. The low activity toward Rab3A was increased to that of Rab1A when the COOH-terminal 12 amino acids of Rab3A were replaced with the corresponding residues of Rab1A. We suggest that REP-2 substitutes for the absent function of REP-1 in nonretinal cells of patients with choroideremia, thus preventing cellular dysfunction throughout the body. In the retina, REP-2 may be only partially effective, leading eventually to retinal degeneration and blindness.
 ...
PMID:REP-2, a Rab escort protein encoded by the choroideremia-like gene. 829 64

Host cell RNA polymerase II (Pol II)-mediated transcription is inhibited by poliovirus infection. This inhibition is correlated to a specific decrease in the activity of a chromatographic fraction which contains the transcription factor TFIID. To investigate the mechanism by which poliovirus infection results in a decrease of TFIID activity, we have analyzed a component of TFIID, the TATA-binding protein (TBP). Using Western immunoblot analysis, we show that TBP is cleaved in poliovirus-infected cells at the same time postinfection as when Pol II transcription is inhibited. Further, we show that one of the cleaved forms of TBP can be reproduced in vitro by incubating TBP with cloned, purified poliovirus encoded protease 3C. Protease 3C is a poliovirus-encoded protease that specifically cleaves glutamine-glycine bonds in the viral polyprotein. The cleavage of TBP by protease 3C occurs directly. Finally, incubation of an uninfected cell-derived TBP-containing fraction (TFIID) with protease 3C results in significant inhibition of Pol II-mediated transcription in vitro. These results demonstrate that a cellular transcription factor can be directly cleaved both in vitro and in vivo by a viral protease and suggest a role of the poliovirus proteinase 3C in host cell Pol II-mediated transcription shutoff.
Mol Cell Biol 1993 Feb
PMID:Direct cleavage of human TATA-binding protein by poliovirus protease 3C in vivo and in vitro. 838 Aug 94

Formation of the 3' ends of RNA polymerase II (Pol II)-specific U small nuclear RNAs (U snRNAs) in vertebrate cells is dependent upon transcription initiation from the U snRNA gene promoter. Moreover, U snRNA promoters are unable to direct the synthesis of functional polyadenylated mRNAs. In this work, we have investigated whether U snRNA 3'-end formation and transcription initiation are also coupled in plants. We have first characterized the requirements for 3'-end formation of an Arabidopsis U2 snRNA expressed in transfected protoplasts of Nicotiana plumbaginifolia. We found that the 3'-end-adjacent sequence CA (N)3-10AGTNNAA, conserved in plant Pol II-specific U snRNA genes, is essential for the 3'-end formation of U2 transcripts and, similar to the vertebrate 3' box, is highly tolerant to mutation. The 3'-flanking regions of an Arabidopsis U5 and a maize U2 snRNA gene can effectively substitute for the Arabidopsis U2 3'-end formation signal, indicating that these signals are functionally equivalent among different Pol II-transcribed snRNA genes. The plant U snRNA 3'-end formation signal can be recognized irrespective of whether transcription initiation occurs at U snRNA or mRNA gene promoters, although efficiency of 3' box utilization is higher when transcription initiation occurs at the U snRNA promoter. Moreover, transcripts initiated from the U2 gene promoter can be spliced and polyadenylated. Transcription from a Pol III-specific plant U snRNA gene promoter is not compatible with polyadenylation. Finally, we reveal that initiation at a Pol II-specific plant U snRNA gene promoter can occur in the absence of the snRNA coding region and a functional snRNA 3'-end formation signal, demonstrating that these sequences play no role in determining the RNA polymerase specificity of plant U snRNA genes.
Mol Cell Biol 1993 Oct
PMID:Activity of chimeric U small nuclear RNA (snRNA)/mRNA genes in transfected protoplasts of Nicotiana plumbaginifolia: U snRNA 3'-end formation and transcription initiation can occur independently in plants. 841 39

The synthesis of ribosomes is an essential cellular process which requires the transcription of the rRNA genes by RNA polymerase I (Pol I). The regulation of rRNA synthesis is known to be coupled to growth regulation. In nongrowing, slowly growing, and rapidly growing Drosophila cells, exposure to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) increases the synthesis of precursor and mature rRNAs. Using nuclear run-on assays, we show that TPA enhances transcription of the rRNA genes. These results suggest that TPA regulates expression of RNA genes transcribed by Pol I, irrespective of the growth state of the cells. In slowly dividing Drosophila cells, increasing the serum concentration rapidly alters the accumulation of rRNA by enhancing rDNA transcription within 1 h. Thus, TPA and serum are each able to rapidly regulate rRNA gene expression in Drosophila cells. These results indicate that the RNA Pol I transcription system can be regulated by agents which have previously been shown to effect specific genes transcribed by the RNA Pol II system.
Mol Cell Biol 1993 Feb
PMID:In vivo regulation of rRNA transcription occurs rapidly in nondividing and dividing Drosophila cells in response to a phorbol ester and serum. 842 12

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum both stimulate rapid increases in the transcription of Drosophila rRNA genes in vivo. Here we report that this stimulation is observed in in vitro transcription assays using nuclear extracts from cells treated with TPA or serum. Experiments in which extracts from TPA- or serum-treated cells were mixed with extracts from cells grown in serum-restricted medium showed that there was an increased RNA polymerase I (Pol I) activity present in the cell extracts from treated cells. We used a series of plasmids that had been deleted in the region 5' to the start site of rRNA transcription to determine which sequences were necessary to support the increased transcription seen in extracts from stimulated cells. DNA templates that contain sequences between -150 and +32 (with +1 as the Pol I transcription start site) show dramatic increases in transcription with TPA- and serum-stimulated cell extracts; however, templates that contain 5' sequences to -60 or -43 show at most one-third of the stimulation level of transcription in nuclear extracts from treated cells in comparison with untreated cell extracts. The 5' deletion to -34 abolishes the stimulation effect and drops the basal-level transcription by 20-fold. These results indicate that the regulation of Pol I transcription in Drosophila cells by serum and TPA requires two DNA elements, sequences from -150 to -60 (upstream control element) and sequences from -43 to -34 (a portion of the core promoter.
Mol Cell Biol 1993 Feb
PMID:In vitro transcription of Drosophila rRNA genes shows stimulation by a phorbol ester and serum. 842 13

We have previously constructed mutants of Saccharomyces cerevisiae in which the gene for the second-largest subunit of RNA polymerase I (Pol I) is deleted. In these mutants, rRNA is synthesized by RNA polymerase II from a hybrid gene consisting of the 35S rRNA coding region fused to the GAL7 promoter on a plasmid. These strains thus grow in galactose but not glucose media. By immunofluorescence microscopy using antibodies against the known nucleolar proteins SSB1 and fibrillarin, we found that the intact crescent-shaped nucleolar structure is absent in these mutants; instead, several granules (called mininucleolar bodies [MNBs]) that stained with these antibodies were seen in the nucleus. Conversion of the intact nucleolar structure to MNBs was also observed in Pol I temperature-sensitive mutants at nonpermissive temperatures. These MNBs may structurally resemble prenucleolar bodies observed in higher eukaryotic cells and may represent a constituent of the normal nucleolus. Furthermore, cells under certain conditions that inhibit rRNA synthesis did not cause conversion of the nucleolus to MNBs. Thus, the role of Pol I in the maintenance of the intact nucleolar structure might include a role as a structural element in addition to (or instead of) a functional role to produce rRNA transcripts. Our study also shows that the intact nucleolar structure is not absolutely required for rRNA processing, ribosome assembly, or cell growth and that MNBs are possibly functional in rRNA processing in the Pol I deletion mutants.
Mol Cell Biol 1993 Apr
PMID:Structural alterations of the nucleolus in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. 845 21

Eukaryotic protein-coding genes are generally transcribed by RNA polymerase II (Pol II), which has a lower transcription rate than that of Pol I. We report here the duplication of two LD1 genes into the rRNA locus and their resultant transcription by Pol I. The multigenic LD1 locus is present in a 2.2-Mb chromosome in all stocks of Leishmania spp. and is also present in multicopy 200- to 450-kb linear chromosomes or multicopy circular DNAs in over 15% of stocks examined. Genomic rearrangement in Leishmania donovani LSB-51.1 resulted in duplication of a 3.9-kb segment of LD1 containing two genes (orfF and orfG) and of a 1.3-kb segment from approximately 10 kb downstream into the rRNA gene repeat region of the 1.2-Mb chromosome. Short sequences (12 or 13 bp) common to the 2.2-Mb LD1 and 1.2-Mb rRNA loci suggest that this gene conversion occurred by homologous recombination. Transcription of the duplicated genes is alpha-amanitin resistant, indicating transcription by Pol I, in contrast to the alpha-amanitin-sensitive (Pol II) transcription of the genes in the 2.2-Mb LD1 locus. This results in higher transcript abundance than expected from the gene copy number in LSB-51.1 and in elevated expression of at least the orfF gene product.
Mol Cell Biol 1995 Dec
PMID:Increased expression of LD1 genes transcribed by RNA polymerase I in Leishmania donovani as a result of duplication into the rRNA gene locus. 852 51

An Alu source gene, called the EPL Alu, was previously isolated by a phylogenetic strategy. Sequences flanking the EPL Alu family member stimulate its RNA polymerase III (Pol III) template activity in vitro. One cis-acting element maps within a 40-nucleotide region immediately upstream to the EPL Alu. This same region contains an Ap1 site which, when mutated, abolishes the transcriptional stimulation provided by this region. The flanking sequence, as assayed by gel mobility shift, forms sequence-specific complexes with several nuclear factors including Ap1. These results demonstrate that an an ancestral Alu source sequence fortuitously acquired positive transcriptional control elements by insertion into the EPL locus, thereby providing biochemical evidence for a model which explains the selective amplification of Alu subfamilies.
J Mol Evol 1996 Jan
PMID:Flanking sequences of an Alu source stimulate transcription in vitro by interacting with sequence-specific transcription factors. 857 61

A novel photoreactive deoxycytidine analog, 4-[N-(p-azidobenzoyl)-2-aminoethyl]-dCTP (ABdCTP), has been synthesized and incorporated at specific sites within the SUP4 tRNA(Tyr) gene. Immobilized single-stranded DNA was annealed to specific oligonucleotides and AB-dCMP incorporated into DNA by primer extension. DNA photoaffinity labeling with AB-dCMP was used to survey protein-DNA contacts in initiation and elongation complexes of RNA polymerase III (Pol III), and compared to DNA photoaffinity labeling using the previously described photoreactive deoxyuridine analog, 5-[N-(pazidobenzoyl)-3-aminoallyl]-dUMP (AB-dUMP) [Bartholomew et al. (1993) Mol. Cell.Biol. 13,942-952]. In contrast to previous studies, we have used a crude protein fraction rather than highly purified preparations of Pol III and transcription factors TFIIIC and TFIIIB to examine if some component of the transcription complex is lost upon purification. Eleven nucleotide positions from bp-17 to bp +17 (+1 being the start site of transcription) on the nontranscribed strand were modified and shown to have little or no effect on transcription complex formation, initiation, or elongation as determined by multiple-round transcription assays. Efficient photoaffinity labeling by DNA containing AB-dCMP gave results comparable to that with AB-dUMP at proximal nucleotide positions and provided new evidence for the placement of the 160 and 31 kDa subunits of Pol III near the 5' end of the transcriptional bubble in an elongation complex. A novel 40 kDa protein was cross-linked at bps -17, -9, and -8 in a TFIIIC-dependent manner that had not been previously detected.
 ...
PMID:Probing the protein-DNA contacts of a yeast RNA polymerase III transcription complex in a crude extract: solid phase synthesis of DNA photoaffinity probes containing a novel photoreactive deoxycytidine analog. 870 56

Full-length copies of a previously described repetitive DNA sequence (CH2-8) were isolated from the genome of the Magnaporthe grisea strain 2539. One copy of the complete element was sequenced and found to resemble a gypsy-like LTR retrotransposon. We named this element MAGGY (MAGnaporthe GYpsy-like element). MAGGY contains two internal ORFs putatively encoding Gag, Pol and Env-like proteins which are similar to peptides encoded by retroelements identified in other filamentous fungi. MAGGY was found to be widely distributed among M. grisea isolates from geographically dispersed locations and different hosts. It was present in high copy number in the genomes of all nine rice-pathogenic isolates examined. By contrast, M. grisea strains isolated from other Gramineae were found to possess varying copy numbers of MAGGY and in some cases the element was completely absent. The wide distribution of MAGGY suggests that this element invaded the genome of M. grisea prior to the evolution of rice-specific form(s). It may since have been horizontally transmitted to other sub-specific groups. One copy of MAGGY, corresponding to the element we sequenced, was located at identical locations in the genomes of geographically dispersed strains, suggesting that this copy of the element is a relatively ancient insertion.
Mol Gen Genet 1996 Jul 26
PMID:MAGGY, a retrotransposon in the genome of the rice blast fungus Magnaporthe grisea. 875 97


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