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

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

The classical and alternative pathway of complement activation are regulated by a series of fluid phase and cell-bound factors, some of which at the same time serve as receptors for fragments of C3 and C4. These molecules are factor H, CR1 (C3b/C4b receptor), CR2 (C3d/EBV receptor), C4BP (C4b binding protein), DAF (decay accelerating factor), MCP (membrane cofactor protein; earlier designated p45/70), CR3 (iC3b receptor or Mac-1) and CR4 (protein 150/95). Due to structural, genetic and functional features these factors are members of one or several newly recognized large families of proteins: (1) molecules with 60 amino acids long repeats (H, CR1, CR2, C4BP, DAF); (2) proteins with 1,2-diacylglycerol membrane anchoring (DAF); (3) proteins with a heterodimer structure and preference for ligands containing the tripeptide arginine-glycine-asparagine (CR3, CR4). Recognizing the above mentioned regulators and receptors of the complement system as belonging to these protein families opens new perspectives for further genetic and functional research of mutual interest to complement and noncomplement scientists.
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PMID:Structural and functional relationships among receptors and regulators of the complement system. 297 57

The nucleotide sequence of a cDNA that encodes a new regulatory subunit, named p45, of the 26S proteasome of human hepatoblastoma HepG2 cells has been determined. The polypeptide predicted from the open reading frame consists of 406 amino acid residues with a calculated molecular weight of 45770 and isoelectric point of 8.35. The sequences of several fragments of bovine p45, determined by protein chemical analyses, spanning 27% of the complete structure, were found to be in excellent accord with those deduced from the human cDNA sequence. Computer analysis showed that p45 belongs to a family of putative ATPases which includes regulatory components of 26S proteasomes. The overall structure of p45 was found to be homologous to that of yeast Sug1p, which has been identified as a transcriptional factor. It is closely similar, but not identical to the sequence reported for Trip1, a functional homolog of Sug1p in human tissues. These results are consistent with the possibility that Sug1-like proteins with distinct sequence function in transcription and protein degradation in human cells. However, the alternative hypothesis, that the same gene locus encodes both p45 and Trip1, cannot be excluded on the basis of such closely similar sequences. In either case, both proteins are likely to function equivalently well in either transcription or protein degradation.
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PMID:cDNA cloning of a new putative ATPase subunit p45 of the human 26S proteasome, a homolog of yeast transcriptional factor Sug1p. 772 37

We have cloned a porcine gene, designated TBP1O, that belongs to the Tat-binding protein/26S protease subunit family. The genomic structure of the porcine TBP1O gene was analyzed after isolation of three overlapping genomic phage lambda clones. The TBP10 gene harbors 12 exons spanning 4.5 kb of chromosomal DNA. The TBP1O gene was assigned to Chromosome (Chr) 12 by fluorescence in situ hybridization (FISH) on metaphase chromosomes. The chromosomal location was confirmed by PCR analysis of a porcine-rodent hybrid cell panel. The TBP1O protein is encoded by a 1221 nucleotide cDNA and has a molecular mass of 45.6 kDa. The predicted amino acid sequence has highest similarity to the human and bovine p45 subunit of the 26S protease and the human transcription factor TRIP1. Further similarities were detected to the slime mold protein DdTBP1O and the Schizosaccharomyces pombe and Saccharomyces cerevisiae protein SUG1. Like DdTBP1O and other members of the protein family, the porcine TBP1O harbors a leucine zipper motif in the N-terminal region and a domain characteristics of ATP-dependent proteases in the C-terminal region.
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PMID:The porcine gene TBP10 encodes a protein homologous to the human tat-binding protein/26S protease subunit family. 883 36

A newly identified nuclear protein rich in leucine heptad repeats called HEC is important for mitosis. To elucidate its mechanism of action, the region containing leucine heptad repeats was used to identify cellular proteins that potentially interact with HEC. Complementary DNAs encoding several proteins including MSS1, p45, Nek2, and Smc1/Smc2, known to be important for G2/M progression, were identified. The interaction between HEC and MSS1, the seventh regulatory subunit of the 26 S proteasome, was further demonstrated by in vitro GST pull-down assays. HEC is not a part of the 26 S proteasome and interacts with MSS1 only when it is dissociated from the complex during M phase. Purified MSS1 specifically hydrolyzes ATP, an activity inhibited by HEC. In addition, HEC inhibits the proteolysis of mitotic cyclin B in vitro. Consistent with this biochemical activity, ectopic expression of HEC inhibits the degradation of mitotic cyclins after telophase, resulting eventually in cell death. These results show that HEC is a negative regulator of MSS1 and suggest that it may modulate M phase progression, in part, through the regulation of proteasome-mediated degradation of cell cycle regulatory proteins.
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PMID:HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins. 929 62

About 40 kilobases (kb) downstream of the rat growth hormone gene, a gene was found to be expressed in the liver and placenta as 1.5 kb poly(A)-rich RNA. Using the genomic DNA fragment as a probe, the corresponding cDNA clone containing a 1.3 kb insert was isolated from the rat liver cDNA library. The deduced amino acid sequence having 406 residues was identical with that of the mouse transcription factor, SUG and human proteasome subunit, p45. The gene was thus identified as the rat SUG/p45 (rSUG/p45) gene. The 5' end of the gene was determined by the primer-extension analysis and the exon was noted to comprise 1409 bases. The rSUG/p45 gene, 6.0 kb in length and possessing 12 exons, started at 42.8 and ended at 36.8 kb downstream from the transcription start site of the GH gene. From exon 2 to 11, the size of each rSUG/p45 exon was identical with the corresponding exon of the 4.4 kb pig gene. Rat SUG/p45 mRNA was similarly expressed in seven different tissues and one cell line.
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PMID:Gene coding for the transcription factor, SUG/proteasome, p45 is located nearly 40 kb downstream from the rat growth hormone gene. 937 Feb 98

In the +27.6 to +36.7 kb downstream region from the transcriptional start site of the rat growth hormone (GH) gene, a gene encoding BAF60b, a component of mammalian SWI/SNF complexes, was found to have the same transcriptional orientation as the GH gene. The 5' end of the BAF60b gene was heterogeneous and the longest gene was 9060 bp long with 13 exons. The largest of all exons was estimated to be 2774 bases. Deduced rat BAF60b protein was made of 531 amino acids and its amino acid sequence was 97% identical with the human counterpart. No TATA box was found up to the -100 bp region but five GC boxes corresponding to the Sp1 binding site were observed up to 640 bp upstream from the transcriptional start site. Sixty-three bases downstream from the BAF60b gene, the polyadenylation site of the gene encoding transcription factor SUG/proteasome p45, whose expression is constant in many tissues, was identified. The BAF60b gene was expressed as 3.0 kb poly(A)-rich RNA in seven tissues and one cell line from rat but its expression varied considerably according to the tissue.
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PMID:Gene structure of rat BAF60b, a component of mammalian SW1/SNF complexes, and its physical linkage to the growth hormone gene and transcription factor SUG/proteasome p45 gene. 942 60

The 26S proteasome is a eukaryotic ATP-dependent protease functioning as a protein death machine. It is a large multisubunit complex, consisting of a catalytic 20S proteasome and two regulatory modules, named PA700. The PA700 complex is composed of multiple subunits of 25-110 kDa, which are classified into two subgroups, a subgroup of at least 6 ATPases that consitute a unique multi-gene family encoding homologous polypeptides conserved during evolution and a subgroup of approximately 15 non-ATPase subunits, most of which are structurally unrelated to each other. In the present study, we report the chromosomal localization and immunological properties of six members of the human 26S proteasomal ATPase family. By use of the fluorescence in situ hybridization method, the S4 (PSMC1), MSS1 (PSMC2), TBP1 (PSMC3), TBP7 (PSMC4), p45 (PSMC5), and p42 (PSMC6) genes were mapped to human chromosomes 19p13.3, 7q22.1-q22.3, 11p11.2, 19q13.11-q13.13, 17q23.1-q23.3, and 12q15, respectively, indicating that the genes for multiple ATPases of the 26S proteasome are located on different chromosomes. Immunoblot analysis revealed that all these ATPases were associated with the purified 26S proteasome and that some of them showed striking heterogeneity in their electrical charges.
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PMID:Chromosomal localization and immunological analysis of a family of human 26S proteasomal ATPases. 947 9

Two activators, named PA700 and PA28, are known to bind to 20 S proteasomes, forming two different complexes. The PA700-proteasome complex, also known as the 26 S proteasome, can degrade intact proteins, whereas complexes with PA28 can degrade only peptides. Monoclonal antibodies to 20 S proteasomes or the p45 ATPase subunit (Trip1, Sug1) of PA700 precipitated the same set of proteins from HeLa extracts, including six different ATPase subunits of PA700. This shows that p45 is not present in other protein complexes and suggests that all 26 S proteasome particles contain the same set of ATPase subunits. Interferons alpha and gamma had no effect on the composition of the 26 S proteasome, except for the replacement of subunits delta, MB1 and Z with Lmp2, Lmp7 and MECL1 respectively. Surprisingly, antibodies to PA28 precipitated p42, a component of PA700. Conversely, anti-p45 antibodies precipitated not only 26 S proteasomes but also PA28 alpha, beta and gamma, indicating that 20 S proteasomes can simultaneously bind both PA700 and PA28. PA28 alpha beta is known to be involved in antigen presentation. Conceivably, intact substrate proteins are recognized by PA700 and fed into proteasomes whose cleavage specificity is optimized for antigen presentation on MHC class I by PA28 and three interferon inducible proteasome subunits.
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PMID:Simultaneous binding of PA28 and PA700 activators to 20 S proteasomes. 962 Aug 78

Proteasomes can exist in several different molecular forms in mammalian cells. The core 20S proteasome, containing the proteolytic sites, binds regulatory complexes at the ends of its cylindrical structure. Together with two 19S ATPase regulatory complexes it forms the 26S proteasome, which is involved in ubiquitin-dependent proteolysis. The 20S proteasome can also bind 11S regulatory complexes (REG, PA28) which play a role in antigen processing, as do the three variable gamma-interferon-inducible catalytic beta-subunits (e.g. LMP7). In the present study, we have investigated the subcellular distribution of the different forms of proteasomes using subunit specific antibodies. Both 20S proteasomes and their 19S regulatory complexes are found in nuclear, cytosolic and microsomal preparations isolated from rat liver. LMP7 was enriched approximately two-fold compared with core alpha-type proteasome subunits in the microsomal preparations. 20S proteasomes were more abundant than 26S proteasomes, both in liver and cultured cell lines. Interestingly, some significant differences were observed in the distribution of different subunits of the 19S regulatory complexes. S12, and to a lesser extent p45, were found to be relatively enriched in nuclear fractions from rat liver, and immunofluorescent labelling of cultured cells with anti-p45 antibodies showed stronger labelling in the nucleus than in the cytoplasm. The REG was found to be localized predominantly in the cytoplasm. Three- to six-fold increases in the level of REG were observed following gamma-interferon treatment of cultured cells but gamma-interferon had no obvious effect on its subcellular distribution. These results demonstrate that different regulatory complexes and subpopulations of proteasomes have different distributions within mammalian cells and, therefore, that the distribution is more complex than has been reported for yeast proteasomes.
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PMID:Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. 1065 52

The transcription factor Sp1 was previously shown to undergo proteasome-dependent degradation when cells were glucose-starved and stimulated with the adenylate cyclase inducer, forskolin. However, the control of the Sp1 degradation process is largely unknown. Using in vitro and in vivo interaction studies, we show in the present study that Sp1 interacts with human Sug1 [hSug1, also known as p45 or thyroid-hormone-receptor interacting protein ('TRIP1')], an ATPase subunit of the 26 S proteasome and a putative transcriptional modulator. This interaction with Sp1 occurs through the C-terminus of hSug1, the region that contains the conserved ATPase domain in this protein. Both in vitro studies, in reconstituted degradation assays, and in vivo experiments, in which hSug1 is overexpressed in normal rat kidney cells, show that full-length hSug1 is able to stimulate the proteasome-dependent degradation of Sp1. However, hSug1 truncations that lack either the N- or C-terminal domain of hSug1 act as dominant negatives, inhibiting Sp1 degradation in vitro. Also, an ATPase mutant of hSug1, while still able to bind Sp1, acts as a dominant negative, blocking Sp1 degradation both in vitro and in vivo. These results demonstrate that hSug1 is involved in the degradation of Sp1 and that ATP hydrolysis by hSug1 is necessary for this process. Our findings indicate that hSug1 is an exchangeable proteasomal component that plays a critical regulatory role in the proteasome-dependent degradation of Sp1. However, hSug1 is not the factor limiting Sp1 degradation in the cells treated with glucosamine. This and other considerations suggest that hSug1 co-operation with other molecules is necessary to target Sp1 for proteasome degradation.
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PMID:Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1. 1081 20


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