Search results for "Secretory protein"
showing 10 items of 29 documents
In vivoanalysis of the lumenal binding protein (BiP) reveals multiple functions of its ATPase domain
2007
International audience; The endoplasmic reticulum (ER) chaperone binding protein (BiP) binds exposed hydrophobic regions of misfolded proteins. Cycles of ATP hydrolysis and nucleotide exchange on the ATPase domain were shown to regulate the function of the ligand-binding domain in vitro. Here we show that ATPase mutants of BiP with defective ATP-hydrolysis (T46G) or ATP-binding (G235D) caused permanent association with a model ligand, but also interfered with the production of secretory, but not cytosolic, proteins in vivo. Furthermore, the negative effect of BiP(T46G) on secretory protein synthesis was rescued by increased levels of wild-type BiP, whereas the G235D mutation was dominant. U…
Identification of Cysteine Ubiquitylation Sites on the Sec23A Protein of the COPII Complex Required for Vesicle Formation from the ER
2017
Background COPII is a multiprotein complex that surrounds carrier vesicles budding from the Endoplasmic Reticulum and allows the recruitment of secretory proteins. The Sec23a protein plays a crucial role in the regulation of the dynamics of COPII formation ensuring the proper function of the secretory pathway. Objective Since few evidences suggest that ubiquitylation could have a role in the COPII regulation, the present study was aimed to establish whether the Sec23a component of the vesicular envelope COPII could be ubiquitylated. Method Sec23a ubiquitylation was revealed by co-immunoprecipitation experiments. Recombinant Sec23a was gel-purified and analyzed by mass spectrometry subjected…
The endoplasmic reticulum unfolded protein response in neurodegenerative disorders and its potential therapeutic significance
2017
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are involved and contribute to neuronal degeneration in several human diseases, including Al…
Avoided motifs: short amino acid strings missing from protein datasets.
2020
Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins…
OSIP1 is a self‐assembling DUF3129 protein required to protect fungal cells from toxins and stressors
2021
International audience; Secreted proteins are key players in fungal physiology and cell protection against external stressing agents and antifungals. Oak stress-induced protein 1 (OSIP1) is a fungal-specific protein with unknown function. By using Podospora anserina and Phanerochaete chrysosporium as models, we combined both in vivo functional approaches and biophysical characterization of OSIP1 recombinant protein. The P. anserina OSIP1(Delta) mutant showed an increased sensitivity to the antifungal caspofungin compared to the wild type. This correlated with the production of a weakened extracellular exopolysaccharide/protein matrix (ECM). Since the recombinant OSIP1 from P. chrysosporium …
Genomic organization and promoter characterization of the gene encoding a putative endoplasmic reticulum chaperone, ERp29
2002
Abstract ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species. The N-terminal domain of ERp29 displays sequence and structural similarity to the protein disulfide isomerase despite the lack of the characteristic double cysteine motif. Although the exact function of ERp29 is not yet known, it was hypothesized that it may facilitate folding and/or export of secretory proteins in/from the ER. ERp29 is induced by ER stress, i.e. accumulation of unfolded proteins in the ER. To gain an insight into the mechanisms regulating ERp29 expression we have cloned and characterized the rat ERp29 gene and studied in details …
The transcriptome of Echinostoma caproni adults: further characterization of the secretome and identification of new potential drug targets.
2013
Abstract Echinostomes are cosmopolitan parasites that infect a large number of different warm-blooded hosts, both in nature and in the laboratory. They also constitute an important group of food-borne trematodes of public health importance mainly in Southeast Asia and the Far East. In addition, echinostomes are an ideal model to study several aspects of intestinal helminth biology, since they present a number of advantages. For example, echinostomes are large worms whose life cycle is relatively easy to maintain in the laboratory. Recently, several studies documented their great value in the study of intestinal helminth–vertebrate host relationship. Detailed knowledge of their genome, trans…
Adult Stem Cell-Derived Extracellular Vesicles in Cancer Treatment: Opportunities and Challenges
2020
Adult stem cells (SCs) participate in tissue repair and homeostasis regulation. The relative ease of SC handling and their therapeutic effect has made of these cell popular candidates for cellular therapy. However, several problems interfere with their clinical application in cancer treatment, like safety issues, unpredictable pro-tumour effects, and tissue entrapment. Therefore cell-free therapies that exhibit SC properties are being investigated. It is now well known that adult SCs exhibit their therapeutic effect via paracrine mechanisms. In addition to secretory proteins, SCs also release extracellular vesicles (EV) that deliver their contents to the target cells. Cancer treatment is on…
Goodpasture Antigen-binding Protein Is a Soluble Exportable Protein That Interacts with Type IV Collagen
2008
Goodpasture-antigen binding protein (GPBP) is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Various studies have questioned these findings and proposed that GPBP serves as transporter of ceramide between the endoplasmic reticulum and the Golgi apparatus. Here we show that cells expressed at least two GPBP isoforms resulting from canonical (77-kDa) and noncanonical (91-kDa) mRNA translation initiation. The 77-kDa polypeptide interacted with type IV collagen and localized as a soluble form in the extracellular compartment. The 91-kDa polypeptide and its derived 120-kDa polypeptide associated with cellular membranes and regulated the extracellular levels of the 77-kD…
Alpha- and gamma-interferon (IFNα, IFNγ) but not interleukin-1 (IL-1) modulate synthesis and secretion of β2-microglobulin by hepatocytes
1988
Soluble serum beta 2-microglobulin has been thought to result from membrane shedding by activated T-lymphocytes. This hypothesis could explain the increase of beta 2-microglobulin serum levels during virally induced mononucleosis, but not elevated levels as observed in other virally induced and in malignant diseases. In this paper we demonstrate that beta 2-microglobulin is a true secretory protein, and that its synthesis in hepatocytes is modulated by IFNs but not by IL-1. While the 45,000 MW HLA antigen can be found only in cell lysates, beta 2-microglobulin is shown to be secreted also into the culture medium like other secretory proteins (e.g. albumin-factor B-complement C3). Furthermor…