Abstract：
:Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 and show that the strength of this interaction determines the efficacy of immunological cross-presentation of the antigenic sequences by APCs. A fluorescein-labeled cytosolic mammalian Hsc70 binding peptide is shown to interact with human Hsp70 molecules with high affinity (K(d) = 0.58 microm at 25 degrees C). Competition experiments demonstrate weaker binding by Hsp70 of antigenic peptides derived from the tumor-associated proteins tyrosinase (K(d) = 32 microm) and melanoma antigen recognized by T cells (MART-1) (K(d) = 2.4 microm). Adding a peptide sequence (pep70) with high Hsp70 binding affinity (K(d) = 0.04 microm) to the tumor-associated peptides enables them to strongly interact with Hsp70. Presentation of tumor-associated peptides by B cells resulting in T cell activation in vitro is enhanced by Hsp70 when the tumor-associated peptides contain the Hsp70 binding sequence. This observation has relevance for vaccine design, as augmented transfer of tumor-associated antigens to APCs is closely linked to the vaccine's efficacy of T cell stimulation.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Pandya MJ,Bendz H,Manzenrieder F,Noessner E,Kessler H,Buchner J,Issels RDdoi
10.1515/BC.2009.038subject
Has Abstractpub_date
2009-04-01 00:00:00pages
305-12issue
4eissn
1431-6730issn
1437-4315pii
10.1515/BC.2009.038journal_volume
390pub_type
杂志文章abstract：:To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the label...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC-2011-170
更新日期：2012-01-01 00:00:00
abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and gluc...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2004.110
更新日期：2004-09-01 00:00:00
abstract：:The surface of spherical, nonporous silica nanoparticles (SiO2-NPs) was modified with gadolinium (Gd) complexes, fluorophores, and cell-penetrating peptides to achieve multifunctionality on a single particle. The Gd surface concentrations were 9-16 μmol/g resulting in nanomaterials with high local longitudinal and tra...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/hsz-2012-0251
更新日期：2013-01-01 00:00:00
abstract：:Mammalian apolipoproteinB (apoB) RNA editing is a site-specific deamination reaction that mediates the C to U conversion responsible for apoB48 production in the mammalian small intestine. This process is not detected in chicken apoB RNA. Mammalian apoB RNA editing is mediated by a multicomponent enzyme complex that i...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/bchm.1998.379.8-9.1075
更新日期：1998-08-01 00:00:00
abstract：:In this work we demonstrate that heat and pressure induce only slightly different energetic changes in the unfolded state of RNase A. Using pressure and temperature as denaturants on a significant number of variants, and by determining the free energy of unfolding at different temperatures, we estimated the stability ...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2006.038
更新日期：2006-03-01 00:00:00
abstract：:Cellular volume regulation is fundamental for numerous physiological processes. The volume-regulated anion channel, VRAC, plays a crucial role in regulatory volume decrease. This channel, which is ubiquitously expressed in vertebrates, has been vastly characterized by electrophysiological means. It opens upon cell swe...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/hsz-2015-0127
更新日期：2015-09-01 00:00:00
abstract：:The ubiquitous calpains, mu- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic N-acetylated 27-mer peptide derived from exon B o...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2003.045
更新日期：2003-03-01 00:00:00
abstract：:TNF-alpha is a major pro-inflammatory cytokine that regulates further cytokine induction, especially of IL-1 and IL-6, in many human diseases including cancer, inflammation and immune disorders. In a search for new inhibitors of inducible TNF-alpha promoter activity and expression, cultures of the imperfect fungus Tri...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2007.066
更新日期：2007-06-01 00:00:00
abstract：:In pancreatic acinar cells stimulation of different intracellular pathways leads to different patterns of Ca2+ signaling. Bombesin induces activation of both phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and phospholipase D (PLD). The latter leads to generation of diacylglycerol (DAG) in ...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.1999.111
更新日期：1999-07-01 00:00:00
abstract：:92 kDa and 72 kDa gelatinases, two neutral proteinases exhibiting elastinolytic activity and secreted as zymogens by aortic smooth muscle cells, were shown to bind to insoluble elastin. The active form of each enzyme interacted with substrate more avidly than latent form. Once bound to insoluble elastin, 92 kDa progel...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/bchm.1997.378.3-4.265
更新日期：1997-03-01 00:00:00
abstract：:MHC (major histocompatibility complex) class I molecules bind intracellular virus-derived peptides in the endoplasmic reticulum (ER) and present them at the cell surface to cytotoxic T lymphocytes. Peptide-free class I molecules at the cell surface, however, could lead to aberrant T cell killing. Therefore, cells ensu...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2004.100
更新日期：2004-09-01 00:00:00
abstract：:In mammalian cells, glucosylceramide (GlcCer), the simplest glycosphingolipid, is hydrolyzed by the lysosomal enzyme acid beta-glucosidase (GlcCerase). In the human metabolic disorder Gaucher disease, GlcCerase activity is significantly decreased owing to one of approximately 200 mutations in the GlcCerase gene. The m...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2008.163
更新日期：2008-11-01 00:00:00
abstract：:Vascular injury triggers endothelial exocytosis of granules, releasing pro-inflammatory and pro-thrombotic mediators into the blood. Nitric oxide (NO) and reactive oxygen species (ROS) limit vascular inflammation and thrombosis by inhibiting endothelial exocytosis. NO decreases exocytosis by regulating the activity of...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2006.173
更新日期：2006-10-01 00:00:00
abstract：:Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We ...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/hsz-2011-0246
更新日期：2012-04-01 00:00:00
abstract：:The GAGA box of the rat serine protease inhibitor 2 (spi 2) genes not only acts as a basal promoter element, but also mediates transcriptional activation by growth hormone and interleukin-6. The GAGA box is separated from the TATA box by only 12 bp, and this close association is required for efficient transcription. H...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2000.127
更新日期：2000-11-01 00:00:00
abstract：:N.BstNBI is a unique restriction endonuclease isolated from Bacillus stearothermophilus. We have characterized the recognition sequence and the cleavage site of N.BstNBI. Mapping of cleavage sites of N.BstNBI showed that it recognizes an asymmetric sequence, 5' GAGTC 3', and cleaves only on the top strand 4 base pairs...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2000.137
更新日期：2000-11-01 00:00:00
abstract：:We have previously described Kunitz-type serine proteinase inhibitors purified from Bauhinia seeds. Human plasma kallikrein shows different susceptibility to those inhibitors. In this communication, we describe the interaction of human plasma kallikrein with fluorogenic and non-fluorogenic peptides based on the Bauhin...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2001.016
更新日期：2001-01-01 00:00:00
abstract：:Low NO concentrations synthesized by constitutively expressed NO synthases act on several signaling pathways activating transcription factors (TF), such as NF-kappaB or AP-1, and thereby influence gene expression. In contrast, during inflammatory reactions the inducible NO synthase produces NO for prolonged periods of...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2003.153
更新日期：2003-10-01 00:00:00
abstract：:The O-acetylation of sialic acids turns out to be one of the most important modifications that influence the diverse biological and pathophysiological properties of glycoconjugates in animals and microorganisms. To understand the functions of this esterification, knowledge of the properties, structures and regulation ...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2003.116
更新日期：2003-07-01 00:00:00
abstract：:The three isoforms of human Ins(1,4,5)P3 3-kinase (IP3K) show remarkable differences in their intracellular targeting. Whereas predominant targeting to the cytoskeleton and endoplasmic reticulum has been shown for IP3K-A and IP3K-B, rat IP3K-C shuttles actively between the nucleus and cytoplasm. In the present study w...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2006.075
更新日期：2006-05-01 00:00:00
abstract：:Studies of extracellular matrix (ECM) biology in the nervous system have mainly focused on laminin, fibronectin and tenascin-R, proteins that are present during nervous system development and normal function. However, during disease, fibrin, which physiologically is not present in the nervous tissue, is detected at ne...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2002.004
更新日期：2002-01-01 00:00:00
abstract：:The lysosomal cysteine proteases cathepsin B and L play important roles in tumor cell invasion. An imbalance between these cathepsins and their endogenous inhibitors, the cystatins, has been associated with development of the metastatic phenotype. Accordingly, many studies have indicated potential use of cystatins in ...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2008.035
更新日期：2008-04-01 00:00:00
abstract：:Bone morphogenetic proteins (BMP) are dimeric factors initiating several distinct signaling cascades by binding to two types of transmembrane serine/threonine kinase receptors (BRI and BRII), and are thus regulating several steps in embryonal development and adult tissue homeostasis. BMP-2 contains two symmetrical pai...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2001.149
更新日期：2001-08-01 00:00:00
abstract：:The stress-activated protein kinase p38/SAPK2 is known to regulate the activity of transcription factors and to control expression of several genes at the transcriptional or post-transcriptional level. In order to identify genes whose expression is under the control of p38/SAPK2 activity, we have compared the mRNA lev...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2000.026
更新日期：2000-03-01 00:00:00
abstract：:Small RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs) or Piwi-interacting RNAs (piRNAs) are important regulators of gene expression in various organisms. Small RNAs bind to a member of the Argonaute protein family and are incorporated into larger structures that mediate diverse gene silencing events. ...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/hsz-2014-0116
更新日期：2014-06-01 00:00:00
abstract：:The glutamyl endopeptidase family of enzymes from staphylococci has been shown to be important virulence determinants of pathogenic family members, such as Staphylococcus aureus. Previous studies have identified the N-terminus and residues from positions 185-195 as potentially important regions that determine the acti...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2010.116
更新日期：2010-10-01 00:00:00
abstract：:Calpain is a calcium-activated non lysosomal neutral thiol protease (EC 3.4.22.17) present in a wide variety of eukaryotic cells. Calpain is usually present as an inactive form and is activated by calcium ions and phospholipids. The ability of calpain to alter, by limited proteolysis, the activity or function of numer...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/BC.2002.079
更新日期：2002-05-01 00:00:00
abstract：:Squamous cell carcinoma antigens (SCCA) 1 and 2 are highly homologous proteins of the serpin family, although they inhibit different types of proteinases. We investigated the expression of both SCCA mRNAs in tumor tissues, in various cell lines (A431, SAS, Ca9, HeLa, SKGIIIa, HSC-2, HSC-3, HSC-4 and KB) and in HSC cel...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2002.136
更新日期：2002-07-01 00:00:00
abstract：:Cathepsin E (CE) is an intracellular aspartic proteinase implicated in various physiological and pathological processes, yet its actual roles in vivo remain elusive. To assess the physiological significance of CE expression in tumor cells, human CE was stably expressed in human prostate carcinoma ALVA101 cells express...
journal_title：Biological chemistry
pub_type： 杂志文章
doi：10.1515/BC.2007.154
更新日期：2007-11-01 00:00:00
abstract：:Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy has emerged as an efficient tool to elucidate the structure and the conformational dynamics of proteins under conditions close to the native state. This review article summarizes the basics as well as the recent p...
journal_title：Biological chemistry
pub_type： 杂志文章,评审
doi：10.1515/hsz-2013-0155
更新日期：2013-10-01 00:00:00
