Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of the first dorsal metacarpal artery flap in the reconstruction of soft tissue defects in 6 patients suffered from severe injuries of the thumb is presented. Detailed description of the operative technique is given and results of the treatment of 3 patients who were examined at 1-2 years after operation are evaluated. All flaps healed uneventfully and defects were covered in all patients without terminalization of the thumb. Functional results were satisfactory in 2 patients, but other one considered his hand incompletely dexter, by means of decreased both total grip and pinch strengths. In the other patient a limited range of motion occurred in MCP joint of the index finger from which the flap was harvested. Sensation of light touch was satisfactory in two patients and decreased in one, and 2PD discrimination was of 10 mm in all 3 patients. Presented technique seems to be useful and relatively safe in the reconstruction of severely injured thumbs, and for rearrangement of sensation within the thumb.
Chir Narzadow Ruchu Ortop Pol 2005
PMID:[The use of first dorsal metacarpal artery flap for thumb reconstruction]. 1602 18

Besides its role as a major recycler of unfolded or otherwise damaged intracellular proteins, the 26S proteasome functions as a regulator of many vital cellular processes and is postulated as a target for antitumor drugs. It has previously been shown that dysfunction of the catalytic core of the 26S proteasome, the 20S proteasome, causes a moderate increase in the frequency of spontaneous mutations in yeast [A. Podlaska, J. McIntyre, A. Skoneczna, E. Sledziewska-Gojska, The link between proteasome activity and postreplication DNA repair in Saccharomyces cerevisiae. Mol. Microbiol. 49 (2003) 1321-1332]. Here we show the results of genetic analysis, which indicate that the mutator phenotype caused by the deletion of UMP1, encoding maturase of 20S proteasome, involves members of the RAD6 epistasis group. The great majority of mutations occurring spontaneously in yeast cells deficient in 20S proteasome function are connected with the unique Rad6/Rad18-dependent error-prone translesion DNA synthesis (TLS) requiring the activities of both TLS polymerases: Pol eta and Pol zeta. Our results suggest the involvement of proteasomal activity in the limitation of this unique error-prone TLS mechanism in wild-type cells. On the other hand, we found that the mutator phenotypes caused by deficiency in Rad18 and Rad6, are largely alleviated by defects in proteasome activities. Since the mutator phenotypes produced by deletion of RAD6 and RAD18 require Pol zeta and Siz1/Ubc9-dependent sumoylation of PCNA, our results suggest that proteasomal dysfunction limits sumoylation-dependent error-prone activity of Pol zeta. Taken together, our findings strongly support the idea that proteolytic activity is involved in modulating the balance between TLS mechanisms functioning during DNA replication in S. cerevisiae.
...
PMID:Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae. 1609 33

Neurodegenerative disorders are characterised by cell damage due to accumulation of toxic, pathologic proteins. Mutations in genes coding different cell proteins result in conformational disturbances of the protein structure, their accumulation and aggregation manifested at the level of light microscope as various intracellular inclusions. This paper is an attempt of approach to cellular mechanisms underlying neurodegenerative diseases of the extrapyramidal system with special attention to ubiquitin-proteasome pathway -- the pathway whose discoverers received the 2004 Nobel Prize in chemistry.
Neurol Neurochir Pol
PMID:[The role of protein conformational disturbances in the pathomechanism of the extrapyramidal system diseases]. 1627 64

The experimental data and the study on human renal tissue in patients with glomerulonephropathies indicate that monocyte chemoattractant protein-1 (MCP-1) plays a main role in progression of inflammatory processes in kidney diseases. Monocytes/macrophages are multifunctional cells that may regulate matrix accumulation by producing transforming growth factor beta-1 (TGF-beta-1), which plays an important role in the progression of renal diseases. The present study was undertaken to evaluate the relationships between the immunoexpression of MCP-1, the number of CD68-positive cells, the immunoexpression of TGF-beta-1 and the extent of renal fibrosis as well serum creatinine level in patients with lupus nephritis. Using immunohistochemistry we analyzed the expression of MCP-1, TGF-beta-1 and the number of CD68+ cells in renal biopsy specimens in 17 patients with IV class of lupus nephritis and in 10 normal kidneys. Statistical analysis revealed significant increase in the tubulointerstitial MCP-beta immunostaining in lupus nephritis as compared to normal controls. In lupus nephritis the amount of glomerular and interstitial CD68+ cells was higher than in control group. None of the control sections have evidence of glomerular or tubulointerstitial immunoexpression of TGF-beta-1. In patients with lupus nephritis TGF-beta-1 was detected in the renal tubular epithelial cells and the interstitium, and to a lesser extent within glomeruli. The tubulointerstitial MCP-1 immunoexpression was significantly correlated with monocyte/macrophage interstitial infiltrates, the immunoexpression of TGF-beta-1 in tubuli and interstitium as well as serum creatinine. Moreover, the tubulointerstitial immunoexpression of TGF-beta-1 was significantly positively correlated with renal interstitial cortical volume and serum creatinine in patients with lupus nephritis. In summary, these data suggest that in lupus nephritis MCP-1 may play a role in modulating interstitial inflammatory process and in tubulointerstitial renal damage via TGF-beta-1 pathway.
Pol J Pathol 2005
PMID:Correlative insights into immunoexpression of monocyte chemoattractant protein-1, transforming growth factor beta-1 and CD68+ cells in lupus nephritis. 1633 78

The proteasome can regulate transcription through proteolytic processing of transcription factors and via gene locus binding, but few targets of proteasomal regulation have been identified. Using genome-wide location analysis and transcriptional profiling in Saccharomyces cerevisiae, we have established which genes are bound and regulated by the proteasome and by Spt23 and Mga2, transcription factors activated by the proteasome. We observed proteasome association with gene sets that are highly transcribed, controlled by the mating type loci, and involved in lipid metabolism. At ribosomal protein (RP) genes, proteasome and RNA polymerase II (RNA Pol II) binding was enriched in a proteasome mutant, indicating a role for the proteasome in dissociating elongation complexes. The genomic occupancies of Spt23 and Mga2 overlapped significantly with the genes bound by the proteasome. Finally, the proteasome acts in two distinct ways, one dependent and one independent of Spt23/Mga2 cleavage, providing evidence for cooperative gene regulation by the proteasome and its substrates.
...
PMID:Genomic association of the proteasome demonstrates overlapping gene regulatory activity with transcription factor substrates. 1654 54

Treatment of Saccharomyces cerevisiae and human cells with DNA-damaging agents such as UV light or 4-nitroquinoline-1-oxide induces polyubiquitylation of the largest RNA polymerase II (Pol II) subunit, Rpb1, which results in rapid Pol II degradation by the proteasome. Here we identify a novel role for the yeast Elc1 protein in mediating Pol II polyubiquitylation and degradation in DNA-damaged yeast cells and propose the involvement of a ubiquitin ligase, of which Elc1 is a component, in this process. In addition, we present genetic evidence for a possible involvement of Elc1 in Rad7-Rad16-dependent nucleotide excision repair (NER) of lesions from the nontranscribed regions of the genome and suggest a role for Elc1 in increasing the proficiency of repair of nontranscribed DNA, where as a component of the Rad7-Rad16-Elc1 ubiquitin ligase, it would promote the efficient turnover of the NER ensemble from the lesion site in a Rad23-19S proteasomal complex-dependent reaction.
...
PMID:Requirement of ELC1 for RNA polymerase II polyubiquitylation and degradation in response to DNA damage in Saccharomyces cerevisiae. 1670 54

The ability of stem cells to activate different gene expression programs requires the choreographed assembly of trans-acting factors at enhancers and promoters during cell differentiation. In this study, we show that the proteasome acts on specific regulatory regions in embryonic stem (ES) cells to prevent incorrect transcriptional initiation. Chemical or siRNA-mediated inhibition of proteasome activity results in increased transcription factor and RNA polymerase II binding and leads to activation of cryptic promoters. Analysis of the binding profiles of different proteasome subunits in normal ES cells and following RNAi knockdown of individual subunits provides evidence for a targeted assembly of the 26S proteasome at specific regulatory elements. Our results suggest that the proteasome promotes a dynamic turnover of transcription factor and Pol II binding at tissue-specific gene domains in ES cells, thereby restricting permissive transcriptional activity and keeping the genes in a potentiated state, ready for activation at later stages.
...
PMID:The proteasome restricts permissive transcription at tissue-specific gene loci in embryonic stem cells. 1719 May 93

The 26S proteasome modulates steroid hormone receptor-dependent gene transcription at least in part by regulating turnover and recycling of receptor/transcriptional DNA complexes, thereby ensuring continued hormone response. For the glucocorticoid receptor (GR), inhibition of proteasome-mediated proteolysis or RNA interference-mediated depletion of specific proteasome subunits results in an increase in gene expression. To facilitate transcription, proteasome inhibition alters at least two features associated with modification of chromatin architecture and gene transcription. First, proteasome inhibition increases trimethyl histone H3K4 levels with a corresponding accumulation of this modification on GR-regulated promoters in vivo. Secondly, global levels of phosphorylated RNA polymerase II (Pol II) increase, together with hormone-dependent association of the phosphorylated Pol II, with the promoter and the body of the activated gene. We propose that apart from modulating receptor turnover, the proteasome directly influences both the transcription machinery and chromatin structure, factors integral to nuclear receptor-regulated gene transcription.
...
PMID:Proteasome activity modulates chromatin modifications and RNA polymerase II phosphorylation to enhance glucocorticoid receptor-mediated transcription. 1743 38

Rpb9, a nonessential subunit of RNA polymerase II (Pol II), has multiple transcription-related functions in Saccharomyces cerevisiae, including transcription elongation and transcription-coupled repair (TCR). Here we show that, in response to UV radiation, Rpb9 also functions in promoting ubiquitylation and degradation of Rpb1, the largest subunit of Pol II. This function of Rpb9 is not affected by any pathways of nucleotide excision repair, including TCR mediated by Rpb9 itself and by Rad26. Rpb9 is composed of three distinct domains: the N-terminal Zn1, the C-terminal Zn2, and the central linker. The Zn2 domain, which is dispensable for transcription elongation and TCR functions, is essential for Rpb9 to promote Rpb1 degradation, whereas the Zn1 and linker domains, which are essential for transcription elongation and TCR functions, play a subsidiary role in Rpb1 degradation. Coimmunoprecipitation analysis suggests that almost the full length of Rpb9 is required for a strong interaction with the core Pol II: deletion of the Zn2 domain causes dramatically weakened interaction, whereas deletion of Zn1 and the linker resulted in undetectable interaction. Furthermore, we show that Rpb1, rather than the whole Pol II complex, is degraded in response to UV radiation and that the degradation is primarily mediated by the 26S proteasome.
...
PMID:Yeast Rpb9 plays an important role in ubiquitylation and degradation of Rpb1 in response to UV-induced DNA damage. 1745 55

This study is the review of 16 hands in the same number of patients (15 men, 1 female) in whom ring finger flexor digitorum superficialis opponensplasty was performed. The patients were operated on during the period of 6 years. The lack of thumb opposition was a result of traumatic nerve leasions (5 median, 11 median and ulnar). The operation was performed 7.2 months (on average) after the nerve reconstruction. The outcome was assessed by scoring the finger to which the thumb could obtain a pinch grip (Kapandji's test), measuring the gap between thumb and little finger MCP joints, the patient's satisfaction. The sensitivity on the pulps of ring and little finger were also tested. Two patients were reoperated for loosening the transferred tendon, two patients developed minor dysfunction of the donor finger. The results were evaluated 41 weeks after an operation. As a result of the operation the "opposition gap" was diminished by 22 mm on average; the patients scoring by Kapandji's test was improved by 2 points. Eight patients assessed the improvement of the hand function as excellent, six as good, two were dissatisfied with the result.
Chir Narzadow Ruchu Ortop Pol 2006
PMID:[Assessment of results of opponensplasty by transfer of flexor digitorum superfitcialis tendon of the ring finger]. 1763 57


<< Previous 1 2 3 4 5 6 Next >>

---