Search results for "sequence data"
showing 10 items of 1952 documents
Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis
2010
Survivin orchestrates intracellular pathways during cell division and apoptosis. Its central function as mitotic regulator and inhibitor of cell death has major implications for tumor cell proliferation. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution a complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulator, a survivin-like protein (SURVL) of one of the earliest-branching metazoan taxa was identified and functionally characterized. SURVL of the sponge Suberites domuncula …
Evidence for an instructive role of apoptosis during the metamorphosis of Hydractinia echinata (Hydrozoa)
2011
Apoptosis is a highly conserved mechanism of cell deletion that destroys redundant, dysfunctional, damaged, and diseased cells. Furthermore, apoptotic cell death is essential during the development of multicellular organisms. However, there are only a few examples where the occurrence of apoptosis has been shown to be a direct prerequisite for developmental processes. As described previously by our group, the degradation of larval tissue during the first half of the metamorphosis of Hydractinia echinata involves extensive cell death. A large number of cells are removed, and we observed several cellular features of apoptotic cell death in the dying tissue, e.g., nucleosomal DNA fragmentation…
Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during verte…
2004
We present seven new vertebrate homologs of the prolactin-releasing hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have…
Inhibition of glycosaminoglycan modification of perlecan domain I by site-directed mutagenesis changes protease sensitivity and laminin-1 binding act…
1998
AbstractGlycosaminoglycan attachment to perlecan domain I (173 residues) was completely prevented by site-directed mutagenesis of Ser-65, Ser-71 and Ser-76 as shown by recombinant production in mammalian cells. This did not interfere with the proper folding of the domain's SEA module but enhanced its sensitivity to neutral proteases. Lack of substitution also abolished binding to the two major heparin binding sites of laminin-1.
Morpholino knockdown of the ubiquitously expressed transmembrane serine protease TMPRSS4a in zebrafish embryos exhibits severe defects in organogenes…
2011
AbstractOver the past years the members of the type II transmembrane serine protease (TTSP) family have emerged as new players in mammalian biology. TMPRSS4 (transmembraneprotease/serine) is overexpressed in several human cancer tissues, promoting invasion, migration, and metastasis. However, the physiological function has not yet been elucidated. Here, we present morpholino knockdown studies targeting TMPRSS4a, a homolog of human TMPRSS4 in zebrafish embryos. By RT-PCR, we could demonstrate an expression of this protease already 5 h post-fertilization, suggesting important functions in the early stages of embryonic development. Indeed,in vivogene silencing caused severe defects in tissue d…
Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the activation kinetics by MMP-3
2012
Abstract Meprin α and β, members of the astacin family of zinc metalloproteinases, are unique plasma membrane and secreted proteases known to cleave a wide range of biological substrates involved in inflammation, cancer and fibrosis. In this study, we identified proMMP-9 as a novel substrate and show that aminoterminal meprin-mediated clipping improves the activation kinetics of proMMP-9 by MMP-3, an efficient activator of proMMP-9. Interestingly, the NH2-terminus LVLFPGDL, generated by incubation with meprin α, is identical to the form produced in conditioned media from human neutrophils and monocytes. Hence, this meprin-mediated processing and enhancement of MMP-9 activation kinetics may …
Metalloprotease meprin β is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding.
2014
Increased expression of metalloprotease meprin β is associated with fibrotic syndromes and Alzheimer's disease (AD). Hence, regulation of meprin activity might be a suitable strategy for the treatment of these conditions. Meprin β is a type 1 transmembrane protein, but can be released from the cell surface by ectodomain shedding. The protease is expressed as an inactive zymogen and requires proteolytic maturation by tryptic serine proteases. In the present study, we demonstrate, for the first time, the differences in the activation of soluble and membrane bound meprin β and suggest transmembrane serine protease 6 [TMPRSS6 or matriptase-2 (MT2)] as a new potent activator, cleaving off the pr…
Specific processing of tenascin-C by the metalloprotease meprinβ neutralizes its inhibition of cell spreading
2009
The metalloprotease meprin has been implicated in tissue remodelling due to its capability to degrade extracellular matrix components. Here, we investigated the susceptibility of tenascin-C to cleavage by meprinbeta and the functional properties of its proteolytic fragments. A set of monoclonal antibodies against chicken and human tenascin-C allowed the mapping of proteolytic fragments generated by meprinbeta. In chicken tenascin-C, meprinbeta processed all three major splicing variants by removal of 10kDa N-terminal and 38kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern was found for large human tenascin-C variant where two N-terminal pep…
Cloning of Sponge (Geodia cydonium) and Tunicate (Botryllus schlosseri) Proteasome Subunit Epsilon (PRCE): Implications about the Vertebrate MHC-Enco…
1996
Proteasomes are large protein complexes that play a major role in selective degradation of intracellular proteins. Eukaryotes feature seven different alpha and beta subunits. Two of the vertebrate housekeeping beta-subunits have MHC-encoded homologues that can substitute for the housekeeping counterparts upon interferon-gamma induction. In the present study we report the cloning of invertebrate beta-subunit proteasome epsilon (PRCE), from the marine sponge Geodia cydonium and from the colonial tunicate Botryllus schlosseri. Sequence comparisons revealed that the sponge and tunicate proteins are strikingly similar to vertebrate and yeast PRCEs and their MHC-linked counterparts the PRCCs (als…
Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses
2006
Differences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cpalpha1), is efficiently generated only by immunoproteasomes. Furthermore, OT-1 mice backcrossed onto low molecular mass protein 7 (LMP7)-deficient mice show a…