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)

Plastid ORF2280 proteins from five species of land plant are shown to have limited amino-acid sequence similarity to a family of proteins that includes the yeast CDC48, SEC18, PAS1 and SUG1 proteins, three subunits of the mammalian 26S protease, and the Escherichia coli FtsH protein. These proteins all contain one or two ATPase domains and many are involved in cell division, transport of proteins across membranes, or proteolysis. Similarity with the ORF2280 proteins is restricted to a single region of about 130 amino acids that contains: (1) sequences resembling a nucleotide binding site but lacking two normally conserved residues, and (2) a downstream conserved motif with the consensus sequence VIX2TX2PX3DPALX2P. Most of the rest of ORF2280 is very poorly conserved among land plants, even though other family members such as CDC48 have slow rates of protein sequence evolution. In contrast, a protein encoded by plastid DNA of the rhodophyte alga Porphyra purpurea is very similar to E. coli FtsH. Phylogenetic analysis suggests that the red and green plastid genes are not true homologues (orthologues) but distinct members of an ancient gene family.
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PMID:Similarity between putative ATP-binding sites in land plant plastid ORF2280 proteins and the FtsH/CDC48 family of ATPases. 808 82

We isolated two mutants from the yeast Saccharomyces cerevisiae, cim3-1 and cim5-1, that arrest cell division in G2/metaphase at 37 degrees C. CIM3 (identical to SUG1; ref. 1) and CIM5 are similar to each other and are members of a family of putative ATPases that have been proposed to be 26S protease subunits. We show here that CIM5 is the functional yeast homologue of the human MSS1 protein and that homologues of CIM3 and CIM5 are present in a highly purified preparation of the Drosophila 26S protease. The short-lived ubiquitin-proline-beta-galactosidase fusion protein is stabilized in cim mutants, but Leu-beta-galactosidase is not. The CLB2 and CLB3 cyclins also accumulate in the cim mutants. Thus the 26S protease is required in vivo for the degradation of ubiquitinated substrates and for anaphase chromosome separation.
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PMID:S. cerevisiae 26S protease mutants arrest cell division in G2/metaphase. 824 32

The SUG1 gene of Saccharomyces cerevisiae encodes a putative ATPase. Mutations in SUG1 were isolated as suppressors of a mutation in the transcriptional activation domain of GAL4. Sug1 was recently proposed to be a subunit of the RNA polymerase II holoenzyme and to mediate the association of transcriptional activators with holoenzyme. We show here that Sug1 is not a subunit of the holoenzyme, at least in its purified form, but of the 26S proteasome, a large complex of relative molecular-mass 2,000K that catalyses the ATP-dependent degradation of ubiquitin-protein conjugates. Sug1 co-purifies with the proteasome in both conventional and nickel-chelate affinity chromatography. Our observations account for the reduced ubiquitin-dependent proteolysis in sug1 mutants and suggest that the effects of sug1 mutations on transcription are indirect results of defective proteolysis.
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PMID:Identification of the gal4 suppressor Sug1 as a subunit of the yeast 26S proteasome. 862 1

In a search for regulatory proteins that interact with the leucine zipper motif of c-Fos in the yeast two-hybrid screen, we have identified a protein (FZA-B) that has extensive sequence similarity to SUG1 of Saccharomyces cerevisiae. Here we show that FZA-B can functionally substitute for SUG1 in yeast and that FZA-B interacts with Fos proteins in vitro through their leucine zippers. In rat liver and in HeLa cells, FZA-B is present in the 26S proteasome complex, as is c-Fos. Immobilized antibody raised against an FZA-B-specific peptide depleted peptidase activity, proteasomal proteins, FZA-B, and c-Fos from a 26S proteasome preparation. FZA-B is found predominantly in the nuclear fraction of COS cells expressing an FZA-B transgene and in the nuclear 26S proteasome of HeLa cells. We conclude that FZA-B is the mammalian homolog of SUG1 (mSug1) and that it is present in the nuclear 26S proteasome of cells. Our results suggest that mSug1 may be involved in the degradation of c-Fos and other transcription factors.
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PMID:Mammalian Sug1 and c-Fos in the nuclear 26S proteasome. 871 Aug 53

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

Using a genetic strategy designed to find proteins involved in the function of the Saccharomyces cerevisiae transcriptional activator GAL4, we isolated mutants in two genes which rescue a class of gal4 activation domain mutants. One of these genes, SUG1, encodes a member of a large family of putative ATPases, the Conserved ATPase containing Domain (CAD) proteins (also known as AAA proteins) that are involved in a wide variety of cellular functions. Subsequently, SUG1 was identified as a subunit of the 26 S proteasome. We have now cloned the gene defined by the second complementation group. SUG2 encodes an essential 49-kDa protein that is also a member of the CAD family and is 43% identical to SUG1. The mutation in sug2-1, like that in sug1-1, is found in the CAD near the highly conserved ATPase motif. We present biochemical and genetic evidence that SUG2 is associated in vivo with SUG1 and is a novel CAD protein subunit of the 26 S proteasome. With its highly conserved mammalian homologs, human p42 and ground squirrel CADp44, SUG2 defines a new class of proteasomal CAD proteins.
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PMID:Isolation and characterization of SUG2. A novel ATPase family component of the yeast 26 S proteasome. 895 18

Yeast SUG1 was originally characterized as a transcriptional mediator for the GAL4 transactivator. A similar role in vertebrates was suggested by the ligand-enhanced interaction between mammalian homologues of yeast SUG1 and the ligand-dependent activating domain (AF-2) of nuclear receptors. SUG1 was also shown to be a component of the PA700 regulatory complex of the 26 S proteasome and a member of a large family of putative ATPases. However, no catalytic function has yet been attributed to SUG1. We show here that SUG1 is a 3'-5' DNA helicase whose activity is dependent on an intact ATP binding domain. The sedimentation heterogeneity of mammalian SUG1 suggests that it may be associated with distinct protein complexes and therefore play multiple roles.
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PMID:SUG1, a putative transcriptional mediator and subunit of the PA700 proteasome regulatory complex, is a DNA helicase. 905 6

Mutations in the basal transcription initiation/DNA repair factor TFIIH are responsible for three human disorders: xeroderma pigmentosum (XP), cockayne syndrome (CS) and trichothiodystrophy (TTD). The non-repair features of CS and TTD are thought to be due to a partial inactivation of the transcription function of the complex. To search for proteins whose interaction with TFIIH subunits is disturbed by mutations in patients we used the yeast two-hybrid system and report the isolation of a novel XPB interacting protein, SUG1. The interaction was validated in vivo and in vitro in the following manner. (i) SUG1 interacts with XPB but not with the other core TFIIH subunits in the two-hybrid assay. (ii) Physical interaction is observed in a baculovirus co-expression system. (iii) In fibroblasts under non-overexpression conditions a portion of SUG1 is bound to the TFIIH holocomplex as deduced from co-purification, immunopurification and nickel-chelate affinity chromatography using functional tagged TFIIH. Furthermore, overexpression of SUG1 in normal fibroblasts induced arrest of transcription and a chromatin collapse in vivo. Interestingly, the interaction was diminished with a mutant form of XPB, thus providing a potential link with the clinical features of XP-B patients. Since SUG1 is an integral component of the 26S proteasome and may be part of the mediator, our findings disclose a SUG1-dependent link between TFIIH and the cellular machinery involved in protein modelling/degradation.
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PMID:The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor. 917 76

SUG1 is an integral component of the 26 S proteasome. Belonging to a novel putative ATPase family, it shares four conserved motifs characteristic of ATP-dependent DNA/RNA helicases. Recombinant rat SUG1 (rSUG1) produced in Escherichia coli was highly purified and characterized in terms of its biochemical properties. The rSUG1 exhibited a Mg2+-dependent ATPase activity. The Km for ATP and Vmax of rSUG1 were 35 microM and 7 pmol of ATP/min/microg of protein, respectively. Both ATPase activity to release [32P]monophosphate and [32P]ATP-labeling activity were coordinately affected by cold ATP severely, GTP and UTP moderately, and CTP little. Interestingly, the rSUG1 ATPase activity was stimulated by poly(U) and poly(C), but not by poly(A), poly(G), or by any forms of DNAs tested. A UV cross-linking assay also indicated poly(U)- and poly(C)-stimulated labeling of rSUG1 with [alpha-32P]ATP. Moreover, the ATPase activity was facilitated by cellular poly(A)+ RNA, but not by poly(A)- RNA. RNA transcribed in vitro from cDNA encoding a b-Zip protein could stimulate the ATPase activity. This is the first report to demonstrate a specific RNA requirement for ATPase with respect to the proteasomal ATPases. Our present work suggests that SUG1 can specifically interact with protein-coding RNA (mRNA) and play some roles in mRNA metabolism.
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PMID:SUG1, a component of the 26 S proteasome, is an ATPase stimulated by specific RNAs. 928 26

In 1988 McCusker and Haber generated a series of mutants which are resistant to the minimum inhibitory concentration of the protein synthesis inhibitor cycloheximide. These cycloheximide-resistant, temperature-sensitive (crl) mutants, in addition, exhibited other pleiotropic phenotypes, e.g., incorrect response to starvation, hypersensitivity against amino acid analogues, and other protein synthesis inhibitors. Temperature sensitivity of one of these mutants, crl3-2, had been found to be suppressed by a mutation, SCL1-1, which resided in an alpha-type subunit of the 20S proteasome. We cloned the CRL3 gene by complementation and found CRL3 to be identical to the SUG1/CIM3 gene coding for a subunit of the 19S cap complex of the 26S proteasome. Another mutation, crl21, revealed to be allelic with the 20S proteasomal gene PRE3. crl3-2 and crl21 mutant cells show significant defects in proteasome-dependent proteolysis, whereas the SCL1-1 suppressor mutation causes partial restoration of crl3-2-induced proteolytic defects. Notably, cycloheximide resistance was also detected for other proteolytically deficient proteasome mutants (pre1-1, pre2-1, pre3-1, pre4-1). Moreover, proteasomal genes were found within genomic sequences of 9 of 13 chromosomal loci to which crl mutations had been mapped. We therefore assume that most if not all crl mutations reside in the proteasome and that phenotypes found are a result of defective protein degradation.
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PMID:Yeast cycloheximide-resistant crl mutants are proteasome mutants defective in protein degradation. 939 70


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