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

The DNA repeats (CTG).(CAG), (CGG).(CCG), (GAA).(TTC), (ATTCT).(AGAAT), and (CCTG).(CAGG), undergo expansion in humans leading to neurodegenerative disease. A genetic assay for repeat instability has revealed that the activities of RecA and RecB during replication restart are involved in a high rate of deletion of (CTG).(CAG) repeats in E. coli. This assay has been applied to (CCTG).(CAGG) repeats associated with myotonic dystrophy type 2 (DM2) that expand to 11 000 copies and to spinocerebellar ataxia type 10 (SCA10) (ATTCT).(AGAAT) repeats that expand to 4500 copies in affected individuals. DM2 (CCTG).(CAGG) repeats show a moderate rate of instability, less than that observed for the myotonic dystrophy type 1 (CTG).(CAG) repeats, while the SCA10 (ATTCT).(AGAAT) repeats were remarkably stable in E. coli. In contrast to (CTG).(CAG) repeats, deletions of the DM2 and SCA10 repeats were not dependent on RecA and RecB, suggesting that replication restart may not be a predominant mechanism by which these repeats undergo deletion. These results suggest that different molecular mechanisms, or pathways, are responsible for the instability of different disease-associated DNA repeats in E. coli. These pathways involve simple replication slippage and various sister strand exchange events leading to deletions or expansions, often associated with plasmid dimerization. The differences in the mechanisms of repeat deletion may result from the differential propensity of these repeats to form various DNA secondary structures and their differential proclivity for primer-template misalignment during replication.
Mol Carcinog 2009 Apr
PMID:Genetic instabilities of (CCTG).(CAGG) and (ATTCT).(AGAAT) disease-associated repeats reveal multiple pathways for repeat deletion. 1930 11

The progesterone receptor (PR) plays important roles in the establishment and maintenance of pregnancy. By dynamic interactions with coregulators, PR represses the expression of genes that increase the contractile activity of myometrium and contribute to the initiation of labor. We have previously shown that PTB-associated RNA splicing factor (PSF) can function as a PR corepressor. In this report, we demonstrated that the PSF heterodimer partner, p54nrb (non-POU-domain-containing, octamer binding protein), can also function as a transcription corepressor, independent of PSF. p54nrb Interacts directly with PR independent of progesterone. In contrast to PSF, p54nrb neither enhances PR protein degradation nor blocks PR binding to DNA. Rather, p54nrb recruits mSin3A through its N terminus to the PR-DNA complex, resulting in an inhibition of PR-mediated transactivation of the progesterone-response element-luciferase reporter gene. PR also repressed transcription of the connexin 43 gene (Gja1), an effect dependent on the presence of an activator protein 1 site within the proximal Gja1 promoter. Mutation of this site abolished PR-mediated repression and decreased the recruitment of PR and p54nrb onto the Gja1 promoter. Furthermore, knockdown p54nrb expression by small interfering RNA alleviated PR-mediated repression on Gja1 transcription, whereas overexpression of p54nrb enhanced it. In the physiological context of pregnancy, p54nrb protein levels decrease with the approach of labor in the rat myometrium. We conclude that p54nrb is a transcriptional corepressor of PR. Decreased expression of p54nrb at the time of labor may act to derepress PR-mediated inhibition on connexin 43 expression and contribute to the initiation of labor.
Mol Endocrinol 2009 Aug
PMID:p54nrb is a transcriptional corepressor of the progesterone receptor that modulates transcription of the labor-associated gene, connexin 43 (Gja1). 1942 54

We investigated the effects of bone marrow-derived mesenchymal stem cells (MSCs) transplantation on the recovery of neurological functions in rat's MCAO (middle cerebral artery occlusion) model and its mechanism. MSCs were isolated from bone marrow of male Sprague Dawley (SD) rats. Female adult SD rats were randomly assigned into 4 groups: sham-operated group, MCAO group, vehicle group and MCAO + MSCs-treated group. MSCs were injected into the lateral ventricle of rats in the MSCs-treated group and the same volume of PBS was given to the vehicle group. The expressions of IL-10 and TNF-alpha were assayed by RT-PCR and ELISA detections at day 1 and 4 after MCAO. The infarction volume was measured by TTC-staining. All rats underwent behavioral tests before, as well as 1, 4, and 14 days after MCAO. MSCs significantly improved functional recovery compared with the control at day 14 after transplantation. Compared with the MCAO group and the vehicle group, the expression of IL-10 mRNA and its protein level in the MSCs group significantly upregulated. However, the expression of TNF-alpha at day 4 after MCAO in the MSCs group significantly decreased compared with that of the MCAO group and the vehicle group. As a result, transplantation with MSCs significantly decreased infarct volume at day 1 and 4. This study strongly suggested transplantation with MSCs could reduce neuronal injury post focal cerebral ischemia in rats partly by regulating the expressions of IL-10 and TNF-alpha in the brain.
Cell Mol Immunol 2009 Jun
PMID:Expression of IL-10 and TNF-alpha in rats with cerebral infarction after transplantation with mesenchymal stem cells. 1956 4

In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post-transcriptional processes. RNA-binding proteins (RBPs) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB (polypyrimidine tract-binding protein) associate with mRNAs encoding hypoxia-response proteins such as HIF-1alpha and VEGF mRNAs, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional RBPs such as iron-response element-binding proteins (IRPs), cytoplasmic polyadenylation-element-binding proteins (CPEBs) and several heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia-regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by RBPs and the mounting interest in targeting hypoxia-regulatory RBPs in diseases with aberrant hypoxic responses.
J Cell Mol Med 2009 Sep
PMID:RNA-binding proteins implicated in the hypoxic response. 1958 5

Recent transcriptome analysis indicates that > 90% of human genes undergo alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-characterized splicing repressor, but PTB knockdown causes both exon inclusion and skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional RNA map now reveal that dominant PTB binding near a competing constitutive splice site generally induces exon inclusion, whereas prevalent binding close to an alternative site often causes exon skipping. This positional effect was further demonstrated by disrupting or creating a PTB-binding site on minigene constructs and testing their responses to PTB knockdown or overexpression. These findings suggest a mechanism for PTB to modulate splice site competition to produce opposite functional consequences, which may be generally applicable to RNA-binding splicing factors to positively or negatively regulate alternative splicing in mammalian cells.
Mol Cell 2009 Dec 25
PMID:Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. 2006 56

The Type I R-M system EcoR124I is encoded by three genes. HsdM is responsible for modification (DNA methylation), HsdS for DNA sequence specificity and HsdR for restriction endonuclease activity. The trimeric methyltransferase (M(2)S) recognises the asymmetric sequence (GAAN(6)RTCG). An engineered R-M system, denoted EcoR124I(NT), has two copies of the N-terminal domain of the HsdS subunit of EcoR124I, instead of a single S subunit with two domains, and recognises the symmetrical sequence GAAN(7)TTC. We investigate the methyltransferase activity of EcoR124I(NT), characterise the enzyme and its subunits by analytical ultracentrifugation and obtain low-resolution structural models from small-angle neutron scattering experiments using contrast variation and selective deuteration of subunits.
J Mol Biol 2010 May 07
PMID:Structural and functional analysis of the engineered type I DNA methyltransferase EcoR124I(NT). 2030 78

To gain global insights into the role of the well-known repressive splicing regulator PTB, we analyzed the consequences of PTB knockdown in HeLa cells using high-density oligonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB-repressed and PTB-activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTB-activated exon to a PTB-repressed exon. Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.
Nat Struct Mol Biol 2010 Sep
PMID:Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. 2071 Nov 88

Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (hsp-32) is a stress induced cytoprotective protein. The present investigation evaluated the capacity of HO-1 to reduce the incidence of reperfusion-induced ventricular fibrillation (VF) and infarct size. HO-1 transgenic (Tg) mice were generated using a rat HO-1 genomic transgene. Isolated mouse hearts obtained from Tg and nontransgenic (NTg) groups were exposed to 20 min of global ischemia and 120 min of reperfusion. Epicardial ECG was recorded to monitor the incidence of reperfusion-induced VF and at the end of the reperfusion period, detection of HO-1 by immunohistochemistry and measurement of infarct size using the TTC method were carried out. Results shown here provide additional support for cardioprotective effects of HO-1 as evidenced by the reduced infarct size. Moreover, overexpression of the HO-1 efficiently reduced the incidence of ischemia/reperfusion (I/R)-induced VF in HO-1 Tg mice.
J Cell Mol Med 2010 Sep
PMID:Reduction of reperfusion-induced ventricular fibrillation and infarct size via heme oxygenase-1 overexpression in isolated mouse hearts. 2071 20

Vanda Mimi Palmer (VMP) is a highly sought as fragrant-orchid hybrid in Malaysia. It is economically important in cosmetic and beauty industries and also a famous potted ornamental plant. To date, no work on fragrance-related genes of vandaceous orchids has been reported from other research groups although the analysis of floral fragrance or volatiles have been extensively studied. An expressed sequence tag (EST) resource was developed for VMP principally to mine any potential fragrance-related expressed sequence tag-simple sequence repeat (EST-SSR) for future development as markers in the identification of fragrant vandaceous orchids endemic to Malaysia. Clustering, annotation and assembling of the ESTs identified 1,196 unigenes which defined 966 singletons and 230 contigs. The VMP dbEST was functionally classified by gene ontology (GO) into three groups: molecular functions (51.2%), cellular components (16.4%) and biological processes (24.6%) while the remaining 7.8% showed no hits with GO identifier. A total of 112 EST-SSR (9.4%) was mined on which at least five units of di-, tri-, tetra-, penta-, or hexa-nucleotide repeats were predicted. The di-nucleotide motif repeats appeared to be the most frequent repeats among the detected SSRs with the AT/TA types as the most abundant among the dimerics, while AAG/TTC, AGA/TCT-type were the most frequent trimerics. The mined EST-SSR is believed to be useful in the development of EST-SSR markers that is applicable in the screening and characterization of fragrance-related transcripts in closely related species.
Mol Biol Rep 2011 Aug
PMID:Development of expressed sequence tag resources for Vanda Mimi Palmer and data mining for EST-SSR. 2111 62

The activity of the glucocorticoid receptor (GR) is modulated by posttranslational modifications, protein stability, and cofactor recruitment. In this report, we investigated the role of the stress-responsive activator of p300/tetratricopeptide repeat domain 5 (TTC5), in the regulation of the GR. TTC5 is a member of the TTC family of proteins and has previously been shown to participate in the cellular response to DNA damage and heat shock. Here, we demonstrate that TTC5 is an important cofactor for the nuclear hormone receptors GR and estrogen receptor. GR and TTC5 interact through multiple tetratricopeptide repeat and LXXLL motifs. TTC5 stabilizes GR and increases its half-life, through a proteasome-dependent process and by inhibiting the actions of the ubiquitin ligase murine double minute 2. Cellular stress, including DNA damage, proteasome inhibition, and heat shock, modulates the interaction pattern of GR/TTC5, thereby altering GR stability and transcriptional activity. Furthermore, GR transcriptional activity is regulated by TTC5 in both a positive and negative fashion under DNA damage conditions in a target gene-specific way. In this report we provide evidence supporting the notion that TTC5 is a novel cofactor regulating GR function in a stress-dependent manner.
Mol Endocrinol 2011 Jan
PMID:Regulation of glucocorticoid receptor activity by a stress responsive transcriptional cofactor. 2114 50


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