Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteasome (multicatalytic proteinase) consists of a large number of non-identical protein subunits which are encoded by the evolutionarily conserved PROS gene family. Using the PROS-Dm35 and PROS-Dm28.1 cDNAs as probes, we have isolated the corresponding genomic DNA clones of Drosophila melanogaster. In situ hybridization shows that the members of the PROS gene family are not organized in a single gene cluster and that, in contrast to the PROS-Dm35 gene, the PROS-Dm28.1 gene is localized on the X chromosome. Analysis of the genomic organization of the PROS-Dm28.1 and PROS-Dm35 genes reveals that both genes are interrupted by two small introns whereby the relative positions of the introns within the two coding regions are not conserved. Neither gene possesses a distinct transcriptional start site as shown by nuclease S1 analysis. Since the promoter regions also do not contain a TATA box, PROS genes appear to be typical house-keeping genes. A putative heat-shock element in the promoter region of the PROS-Dm35 gene was shown to be inactive on stress induction when fused to a reporter gene and tested in transient transfections assays. In addition, promoter deletion analysis demonstrates that the promoter region between positions -605 and -330 contains sequence elements important for PROS-Dm35 gene activity and that deletions beyond position -150 result in an almost complete inhibition of transcription.
 ...
PMID:Molecular characterization of the genomic regions of the Drosophila alpha-type subunit proteasome genes PROS-Dm28.1 and PROS-Dm35. 137 31

A cDNA clone isolated from an Arabidopsis thaliana cell suspension culture library showed considerable similarities to the proteasome 28 kDa alpha subunit of Drosophila [(1990) Gene 90, 235-241]. The 250 amino acid-long protein encoded by Arabidopsis TAS-g64 clone has important homologies in its primary structure and in the predicted secondary structure with the PROS-28.1 clone from Drosophila. The only divergence observed between the two sequences is for the 20 C-terminal amino acids. This subunit might share important functions in both kingdoms, as revealed by the important conservation between plants and animals. In plant cells it is encoded by a single-copy gene and probably regulated by stress and/of division.
 ...
PMID:Cloning and sequence analysis of a cDNA clone from Arabidopsis thaliana homologous to a proteasome alpha subunit from Drosophila. 151 3

In the present communication, we report the identification of a new gene family which encodes the protein subunits of the proteasome. The proteasome is a high-Mr complex possessing proteolytic activity. Screening a Drosophila lambda gt11 cDNA expression library with the proteasome-specific antibody N19-28 we isolated a clone encoding the 28-kDa No. 1 proteasome protein subunit. In accordance with the nomenclature of proteasome subunits in Drosophila, the corresponding gene is designated PROS-28.1, and it encodes an mRNA of 1.1 kb with an open reading frame of 249 amino acids (aa). Genomic Southern-blot hybridization shows PROS-28.1 to be a member of a family of related genes. Analysis of the predicted aa sequence reveals a potential nuclear targeting signal, a potential site for tyrosine kinase and a potential cAMP/cGMP-dependent phosphorylation site. The aa sequence comparison of the products of PROS-28.1 and PROS-35 with the C2 proteasome subunit of rat shows a strong sequence similarity between the different proteasome subunits. The data suggest that at least a subset of the proteasome-encoding genes belongs to a family of related genes (PROS gene family) which may have evolved from a common ancestral PROS gene.
 ...
PMID:The Drosophila PROS-28.1 gene is a member of the proteasome gene family. 216 43

The proteasome is a multicatalytic proteinase complex composed of nonidentical protein subunits. We have isolated a cDNA clone encoding the 35 kd proteasome subunit of Drosophila melanogaster and propose the designation PROS-35 for the corresponding gene. The deduced amino acid sequence reveals a region of striking homology to a tyrosine phosphorylation site of viral and cellular proteins suggesting a potential regulatory function for the 35 kd subunit within the proteinase complex. Immunocytochemical experiments reveal a tissue-dependent differential distribution of the proteasome between the nucleus and cytoplasm. In addition developmental analysis shows that the proteasome is highly expressed in the CNS of stage-16 embryos and in cardia, ventriculus and ovaries of adult flies. These data suggest a tissue- and development-dependent distribution of the proteasome in D. melanogaster.
 ...
PMID:The PROS-35 gene encodes the 35 kd protein subunit of Drosophila melanogaster proteasome. 247 45

The proteasome is a multisubunit 20 S proteinase complex involved in ubiquitin-dependent and -independent intracellular protein metabolism. Individual subunits of the alpha- and beta-type share extensive sequence homology and are encoded as members of two related and evolutionarily conserved gene families. Due to the lack of viable deletion mutants of essential alpha-type proteasome subunits in higher eukaryotes, an identification and analysis of potentially homologous subunits of different species was so far not possible. It is shown here that the novel Drosophila alpha-type Dm25 subunit can be incorporated into mouse proteasomes of stably transfected NIH 3T3 cells. The Dm25 subunit is able to substitute the mouse MC3 alpha-type subunit in proteasomes, indicating a high structural and possibly also functional homology of the two subunits. In contrast and pointing at the importance of the slightly hydrophobic N-terminal region stabile expression of a Dm25 subunit, which is truncated at its N terminus and lacks PROS box I, results in a subunit which cannot be incorporated into mouse proteasomes. The ability to form hybrid proteasomes involving essential nondeletable subunits now opens the possibility for structural and also functional analysis of such subunits by mutagenesis in higher eukaryotes.
 ...
PMID:Drosophila proteasome Dm25 subunit substitutes the mouse MC3 subunit in hybrid proteasomes. The N-terminal domain is essential for subunit incorporation. 824 93

The 20S proteasome is widely viewed at as a cytoplasmic multicatalytic proteinase complex: immunocytochemical investigations, however, show that proteasomes are localized in the cytoplasm as well as in the nucleus within the same cell. Strong nuclear accumulation of proteasomes is observed in rapidly dividing cells such as in the early stages of Drosophila embryogenesis and in tumorigenic cells. In fact, dependent on the metabolic state of a certain tissue or cell type its cellular distribution appears differentially regulated. Several of the proteasomal alpha-type subunits carry putative nuclear localization signals which may or may not take part in the regulation of the intracellular distribution of 20S proteasomes. We have examined the functional role of the putative nuclear localization signal (NLS) -KKKQKK-in the Drosophila PROS-28.1 subunit by deletion mutagenesis and transfection experiments. Linkage of the putative PROS-28.1 NLS to BSA as reporter protein and in vitro import studies with permeabilized mouse NIH 3T3 cells show that this NLS is able to induce complete translocation of the reporter protein into the cell nucleus. For analysis of the NLS within the 28-kDa subunit, cDNA deletion constructs were cloned into a pSG5 expression vector and transiently transfected into mouse fibroblast cells. Whereas the deletion of the NLS alone resulted only in a slight impairment of subunit transport into the nucleus, removal of the C-terminal 96 amino acid residues abolished nuclear translocation completely.
 ...
PMID:Functional analysis of eukaryotic 20S proteasome nuclear localization signal. 863 18

Removal of cardiac neural crest disrupts normal development of the heart and pharynx. Subtractive hybridization was used to identify differentially expressed messages after neural crest ablation in chick embryos. A 1 kb clone, homologous to PROS-28, a 28 kD alpha subunit of a Drosophila proteasome, was differentially expressed in embryos lacking neural crest. An increase of GPROS-28 expression in the head and pharyngeal arches of stages 12-21 chick embryos without cardiac neural crest accompanied generalized low-level expression throughout experimental and normal embryos. In addition, high levels of GPROS-28 expression were detected in normal embryos at particular sites and times in development in the limb buds, mesonephros, heart, liver, neural tube, dorsal root ganglia, and lung buds, when the cells in these regions were undergoing intense proliferation.
 ...
PMID:Differential expression of a proteasomal subunit during chick development. 916 92

A TG dinucleotide repeat was identified in intron 6 of the human proteasome core particle PROS-27K (IOTA, PSMA6) gene. We present data on the length polymorphism of this repeat in 120 individuals from Latvia and 197 individuals from Finland. A combination of PCR and fluorescent gel electrophoresis was utilized to type the polymorphism. Twelve alleles were observed, varying in length from 10 to 23 TG repeats. Similar allele frequencies were observed in Latvian and Finnish subjects, with 17 and 20 repeats being the most frequent in both populations. We suggest that this TG dinucleotide repeat could be utilized as a prospective marker for genetic linkage and association studies of common diseases.
 ...
PMID:Identification of an intronic TG repeat polymorphism in the human proteasome core particle PROS-27K gene. 1239 23

The Anopheles gambiae cDNA encoding the homologue of the Drosophila melanogaster proteasome PROS-Dm25 was identified and analysed in terms of nucleotide sequence, and chromosomal localisation. In the 3' untranslated region, a GA-rich sequence was mapped which was found to be widely polymorphic among taxa belonging to the A. gambiae complex.
 ...
PMID:Genetic differentiation at the 3'UTR of PROS-Ag25: a cDNA homologue of Drosophila melanogaster proteasome subunit PROS-Dm25 in the malaria vector Anopheles gambiae. 1273 68