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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 DNA binding activity of the dimeric sequence-specific transcription factor NF-kappa B can be controlled by a variety of post-translational mechanisms, including interactions with inhibitor proteins and by its redox state. The NF-kappa B family of transcription factors bind to kappa B motif sequences found in promoter and enhancer regions of a wide range of cellular and viral genes. Normally NF-kappa B family proteins are held in the cytoplasm in an inactive, non-DNA binding form by labile I kappa B inhibitor proteins. When the cell is activated by one of a wide range of stimuli, typically those associated with the cellular response to pathogens or stress, proteolytic degradation of I kappa B inhibitor proteins allows active NF-kappa B to translocate to the nucleus where it activates transcription of responsive genes. The initial trigger for I kappa B degradation is a signal-induced site-specific phosphorylation by an as yet unidentified kinase, which appears to target I kappa B for the covalent addition of multiple copies of the ubiquitin polypeptide. This modification subsequently allows the proteolytic degradation of the ubiquitinated I kappa B by the cellular 26S multicatalytic proteinase (proteasome) complex. It was recently shown that increased I kappa B-alpha expression in the cytoplasm leads to I kappa B-alpha accumulating in the nuclear compartment, removing template-bound NF-kappa B, and reducing NF-kappa B-dependent transcription. These NF-kappa B-I kappa B-alpha complexes could then be actively re-exported to the cytoplasm, allowing the cell to respond to further stimuli.
Int J Biochem Cell Biol 1995 Sep
PMID:Regulation of the DNA binding activity of NF-kappa B. 758 22

The 20S proteasome is the enzyme complex responsible for the processing of antigens bound by major histocompatibility complex class I molecules. The role of the interferon-gamma (IFN-gamma)-inducible proteasome subunits LMP2 and LMP7 in this process is, however, still controversial. We have studied the effects of IFN-gamma-independent LMP incorporation on the quality of peptides processed from the murine cytomegalovirus IE pp89 25-mer polypeptide substrate through dual cleavages by 20S proteasomes. The incorporation of a single LMP subunit or both LMP2 and LMP7 induces changes in 20S proteasome subunit stoichiometry, alters its cleavage site preference and in consequence, the quality of the generated peptides. When the several hydrolytic activities are tested with short fluorogenic peptide substrates, the Vmax, S0.5 (Km), or both values of 20S proteasomes are altered, depending on the combination of LMP. There exists, however, no obvious correlation between the observed changes in hydrolytic activities against short fluorogenic peptides and the changes in dual cleavage site usage within the 25-mer polypeptide substrate. As judged from the calculated Hill coefficients, the presence of both LMP subunits induces a drastic increase in positive cooperativity between the proteasome subunits.
Eur J Immunol 1995 Sep
PMID:Incorporation of major histocompatibility complex--encoded subunits LMP2 and LMP7 changes the quality of the 20S proteasome polypeptide processing products independent of interferon-gamma. 758 33

Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that bind to specific structures, termed iron-responsive elements (IREs), that are located in the 5'- or 3'-untranslated regions of mRNAs that encode proteins involved in iron homeostasis. IRP1 and IRP2 RNA binding activities are regulated by iron; IRP1 and IRP2 bind IREs with high affinity in iron-depleted cells and with low affinity in iron-repleted cells. The decrease in IRP1 RNA binding activity occurs by a switch between apoprotein and 4Fe-4S forms, without changes in IRP1 levels, whereas the decrease in IRP2 RNA binding activity reflects a reduction in IRP2 levels. To determine the mechanism by which iron decreases IRP2 levels, we studied IRP2 regulation by iron in rat hepatoma and human HeLa cells. The iron-dependent decrease in IRP2 levels was not due to a decrease in the amount of IRP2 mRNA or to a decrease in the rate of IRP2 synthesis. Pulse-chase experiments demonstrated that iron resulted in a 3-fold increase in the degradation rate of IRP2. IRP2 degradation depends on protein synthesis, but not transcription, suggesting a requirement for a labile protein. IRP2 degradation is not prevented by lysosomal inhibitors or calpain II inhibitors, but is prevented by inhibitors that block proteasome function. These data suggest the involvement of the proteasome in iron-mediated IRP2 proteolysis.
J Biol Chem 1995 Sep 15
PMID:Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. 766 79

In most cases, the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits, p50 and p65, which are encoded by two distinct genes of the Rel family. p50 is translated as a precursor of 105 kDa. The C-terminal domain of the precursor is rapidly degraded, forming the mature p50 subunit consisted of the N-terminal region of the molecule. The mechanism of generation of p50 is not known. It has been suggested that the ubiquitin-proteasome system is involved in the process; however, the specific enzymes involved and the mechanism of limited proteolysis, in which half of the molecule is spared, have been obscure. Palombella and colleagues (Palombella, V. J., Rando, O. J., Goldberg, A. L., and Maniatis, T. (1994) Cell 78, 773-785) have shown that ubiquitin is required for the processing in a cell-free system of a truncated, artificially constructed, 60-kDa precursor. They have also shown that proteasome inhibitors block the processing both in vitro and in vivo. In this study, we demonstrate reconstitution of a cell-free processing system and demonstrate directly that: (a) the ubiquitin-proteasome system is involved in processing of the intact p105 precursor, (b) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing, (c) the recently discovered novel species of the ubiquitin-carrier protein, E2-F1, that is involved in the conjugation and degradation of p53, is also required for the limited processing of the p105 precursor, and (d) a novel, approximately 320-kDa species of ubiquitin-protein ligase, is involved in the process. This novel enzyme is distinct from E6-AP, the p53-conjugating ligase, and from E3 alpha, the "N-end rule" ligase.
J Biol Chem 1995 Sep 15
PMID:Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105. Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation. 766 88

Polyacrylamide gel electrophoresis and high performance liquid chromatography of multicatalytic proteinase complexes (MPC) isolated from bovine pituitary, lung, and liver showed marked differences in the pattern of subunits. The concentrations of LMP7 in the lung and liver were 10 and 5 times, respectively, greater than those in the pituitary, whereas the chymotrypsin-like activity and the amount of a subunit (BO2), necessary for its expression, were markedly decreased in the lung and moderately decreased in the liver. Lower trypsin-like, small neutral amino acid preferring, and peptidyl-glutamyl-peptide hydrolyzing activities were also found in the lung and liver. The activity of the branched chain amino acid preferring component (BrAAP), predominantly latent in the pituitary, was highly activated in the lung and liver, as evidenced by a greatly decreased Km and a 20-fold increase of the specificity constant Vmax/Km, indicating facilitated substrate access to its active site and increased affinity toward substrates with branched chain amino acids in the P1 position. It is suggested that overexpression of LMP7 in the lung is related to increased exposure of the airways to foreign antigens. The possible association between amounts of LMP7 and the activation of the BrAAP component needs further examination.
J Biol Chem 1995 Sep 22
PMID:Differences in catalytic activities and subunit pattern of multicatalytic proteinase complexes (proteasomes) isolated from bovine pituitary, lung, and liver. Changes in LMP7 and the component necessary for expression of the chymotrypsin-like activity. 767 55

The tax gene product of the human T-cell leukemia virus type I (HTLV-I) induces the nuclear expression and biological function of the NF-kappa B/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-kappa B/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of I kappa B alpha in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of I kappa B alpha requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of I kappa B alpha, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of I kappa B alpha observed in HTLV-I-infected T cells. Interestingly, inhibition of I kappa B alpha degradation in these cells led to the accumulation of a phosphorylated form of I kappa B alpha. Together, these studies suggest that Tax activation of NF-kappa B/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor I kappa B alpha.
Oncogene 1995 Sep 07
PMID:Activation of NF-kappa B/Rel by Tax involves degradation of I kappa B alpha and is blocked by a proteasome inhibitor. 767 60

In this report, we have shown the expression of the complement regulatory proteins decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 on human D54-MG astroglioma cells by several methods, including immunofluorescence, flow cytometry and Western blotting and Northern blot analysis. These studies demonstrate that all three proteins are structurally and antigenically similar to their counterparts expressed on HepG2 and SW480 cells (hepatocyte and epithelial cell lines, respectively). D54-MG cells express mRNA for all three proteins of the appropriate size(s). The phosphatidylinositol-specific enzyme, PIPLC, cleaved DAF from the surface of D54-MG cells, demonstrating that DAF is linked by a glycophospholipid anchor as has been shown for other cell types. Flow cytometry demonstrates that primary rat astrocytes also constitutively express all three regulatory proteins. These data are the first to demonstrate the expression of CD59 on astrocytes, and the presence of all three regulatory proteins on astrocytes suggests that regulation of complement activation in the central nervous system is important in neural host defense mechanisms.
J Neuroimmunol 1993 Sep
PMID:Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes. 769 Mar 70

There is accumulating evidence for a large, highly conserved gene family of putative ATPases. We have identified 12 different members of this novel gene family (the YTA family) in yeast and determined the nucleotide sequences of nine of these genes. All of the putative gene products are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of ATPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to proteins involved in human immunodeficiency virus Tat-mediated gene expression but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of human TBP-1 can compensate for the loss of YTA1. Preliminary experiments indicate that YTA1 is a component of the 26S protease complex from yeast. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 function as regulatory subunits of the yeast 26S proteasome. YTA10, YTA11 and YTA12 share significant homology with the Escherichia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate subclass within this family of putative ATPases.
Yeast 1994 Sep
PMID:Identification of a set of yeast genes coding for a novel family of putative ATPases with high similarity to constituents of the 26S protease complex. 775 4

CD46 (membrane cofactor protein; MCP) is ubiquitously expressed on nucleated human cells; it has a protective function, binding C3b and C4b, which are then cleaved by serum factor I. CD46 molecules (55,000-65,000 MW) have four short consensus repeats (SCR): the function of SCR-1 and -2 is unknown; SCR-3 and -4 bind C3b and C4b. These are succeeded by the STP region, which can contain three separate regions (STP-A, -B, -C) rich in serine, threonine and proline and which are heavily glycosylated, succeeded by transmembrane and cytoplasmic tail regions (of which there are several). Multiple isoforms exist due to the different splicing of exons: STP-A and -B can thus be present or absent. So far these products can only be detected separately by polymerase chain reaction (PCR) and RNA studies; we now describe their detection by anti-peptide antibodies. Peptides whose sequences corresponded with those of STP-A and STP-B were synthesized and used for the immunization of mice; although they differ in only seven of 21 amino acids, monoclonal antibodies (mAb) that reacted specifically with STP-A but not with STP-B, and mAb that reacted specifically with STP-B but not with STP-A, were produced; these reacted specifically with native CD46 on human tissues and cell lines. STP-A mAb reacted with tissues in which STP-A RNA had been found, some leukaemias and cell lines; in normal tissue expression was mainly found in the intestine (large and small) and salivary gland. Anti-STP-B reacted with most tissues and cell lines. The antibodies should be of use in defining the expression and function of CD46 in different tissues.
Immunology 1994 Sep
PMID:Discrimination between alternatively spliced STP-A and -B isoforms of CD46. 782 56

Prosomes, also called "multicatalytic proteinase" or proteasomes, were purified from chick embryos of different developmental stages by a simple, single-step procedure. These were characterized by their characteristic protein patterns determined by SDS polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting with four monoclonal antibodies, namely, anti-p27, -p28, -p29 and -p31, prepared against duck prosomes. In vitro labeling of embryos with 35S-methionine followed by SDS PAGE and fluorography of the purified prosomes revealed that their polypeptides are differentially synthesized at various stages during development. Among 12 polypeptides (p21 to p56), p21 is synthesized at the beginning of gastrulation (stage 2) followed by the synthesis of p24 at stage 3. Nine other polypeptides (p25 to p35) are synthesized at the head-fold stage (stage 6), while the synthesis of polypeptide p56 is only detected at stage 10 (10-somite stage). Indirect immunofluorescence studies, with the 4 monoclonal antibodies, demonstrated 3 distinct, developmental stage-specific patterns of cytodistribution of these four prosome polypeptides in the embryos. During early embryogenesis, these are uniformly nuclear in location, while at later stages (stage 4 onwards) they are also present in the cytoplasm. Interestingly, one of the antigens (p 28), although found uniformly in all types of tissues in the embryos up to the gastrulation stage, is undetectable in the neural tissues and nonuniformly distributed in other tissues of stage-10 embryos. These data suggest that there are subcomponents of prosomes which are synthesized as well as distributed in an independent manner during development, possibly reflecting subcomponent-specific multiple functions of these particles.
Int J Dev Biol 1994 Sep
PMID:Differential synthesis and cytolocalization of prosomes in chick embryos during development. 784 36


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