Regulation of calreticulin gene expression by calcium<...
TY - JOUR. T1 - Regulation of calreticulin gene expression by calcium. AU - Waser, Mathilde. AU - Mesaeli, Nasrin. AU - Spencer, Charlotte. AU - Michalak, Marek. PY - 1997/8/11. Y1 - 1997/8/11. N2 - We have isolated and characterized a 12-kb mouse genomic DNA fragment containing the entire calreticulin gene and 2.14 kb of the promoter region. The mouse calreticulin gene consists of nine exons and eight introns, and it spans 4.2 kb of genomic DNA. A 1.8-kb fragment of the calreticulin promoter was subcloned into a reporter gene plasmid containing chloramphenicol acetyltransferase. This construct was then used in transient and stable transfection of NIH/3T3 cells. Treatment of transfected cells either with the Ca2+ ionophore A23187, or with the ER Ca2+-ATPase inhibitor thapsigargin, resulted in a five- to sevenfold increase of the expression of chloramphenicol acetyltransferase protein. Transactivation of the calreticulin promoter was also increased by fourfold in NIH/3T3 cells treated with ...
Recombinant Human Calreticulin protein (ab40609) | Abcam
Buy our Recombinant Human Calreticulin protein. Ab40609 is a protein fragment produced in Escherichia coli and has been validated in SDS-PAGE, MS. Abcam…
Anti-Calreticulin Antibody | 06-661
Anti-Calreticulin Antibody is an antibody against Calreticulin for use in IC, IH & WB. Find MSDS or SDS, a COA, data sheets and more information.
Toxins | Free Full-Text | SS1P Immunotoxin Induces Markers of Immunogenic Cell Death and Enhances the Effect of the CTLA-4...
SS1P is an anti-mesothelin immunotoxin composed of a targeting antibody fragment genetically fused to a truncated fragment of Pseudomonas exotoxin A. Delayed responses reported in mesothelioma patients receiving SS1P suggest that anti-tumor immunity is induced. The goal of this study is to evaluate if SS1P therapy renders mesothelioma tumors more sensitive to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade. We evaluated the ability of SS1P to induce adenosine triphosphate (ATP) secretion and calreticulin expression on the surface of AE17M mouse mesothelioma cells. Both properties are associated with immunogenic cell death. Furthermore, we treated these tumors with intra-tumoral SS1P and systemic CTLA-4. We found that SS1P increased the release of ATP from AE17M cells in a dose and time-dependent manner. In addition, SS1P induced calreticulin expression on the surface of AE17M cells. These results suggest that SS1P promotes immunogenic cell death and could sensitize tumors
Functional Analysis of Recombinant Calreticulin Fragment 39-272: Implications for Immunobiological Activities of Calreticulin...
Although calreticulin (CRT) is a major Ca2+-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39-272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39-272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4-dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in ...
Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth | JEM
These results show that vasostatin, an NH2-terminal fragment of human calreticulin, can inhibit endothelial cell proliferation in vitro, suppress neovascularization in vivo, and prevent or reduce growth of experimental tumors. Calreticulin, a ubiquitous and highly conserved protein originally identified in skeletal muscle sarcoplasmic reticulum, serves as one of the major storage depots for calcium ions within the endoplasmic reticulum and participates in calcium signaling ((34)-(36)). The NH2-domain of calreticulin, which includes aa 1-180, is the most conserved domain among the calreticulins so far cloned and has no homology to other protein sequences ((34), (35)). Although it does not bind calcium, it can bind the cytoplasmic domain of α subunits of integrins regulating cell attachment ((37)), can interact with the nuclear receptors for glucocorticoid, androgen, and retinoic acid, regulating their binding to DNA ((38)), and can, once phosphorylated, bind stem-loop structures at the 3′-end ...
anti-Calreticulin antibody | GeneTex
Calreticulin antibody (calreticulin) for ICC/IF, IHC-P, WB. Anti-Calreticulin pAb (GTX111627) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
Enhanced EGFR expression and function in calreticulin deficient cells | QScience.com
Abstract
Introduction:
Calreticulin is a multi-functioning protein located in the endoplasmic reticulum. Several functions have been attributed to calreticulin including lectin-like chaperoning, regulation of gene expression, cell adhesion, auto-immunity and calcium homeostasis. As an endoplasmic reticulum chaperone calreticulin regulates the maturation and folding of several trans-membrane proteins. We hypothesized that as an endoplasmic reticular protein it regulates the expression folding and maturation of epidermal growth factor receptor (EGFR). To date no information is available about the role of calreticulin in EGFR expression and folding.
Methods:
Wild type calreticulin deficient (crt -/-) and mouse lung cancer cells isolated from transgenic mice over expressing calreticulin was used to examine the expression, localization and function of EGFR. Western blot analysis was used to determine the protein expression. Immunocytochemical staining of cells was utilized to determine localization of EGFR
Ca2+ release in saponin-permeabilized calreticulin-defi | Open-i
Ca2+ release in saponin-permeabilized calreticulin-deficient cells. Wild-type (K41) and calreticulin-deficient (K42) cells were loaded with a fluorescent Ca2+ i
JCI - Welcome
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1. Here, we observed antitumor activity following combinatorial therapy with anti-PD1 Ab and the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor models. Dinaciclib induced a type I IFN gene signature within the tumor, leading us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by eliciting ICD. Indeed, tumor cells treated with dinaciclib showed the hallmarks of ICD including surface calreticulin expression and release of high ...
Dokument bez názvu
Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification and modification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexin have similar substrate specificity and share several common features. Yet, surprisingly, mice bearing a disruption in the calreticulin gene die from a lesion in cardiac development and develop significant metabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurological problems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexindeficient cell lines indicate that calnexin is unable to compensate for the loss of calreticulin and conversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency or reduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolic disorders as documented by sever changes serum lipids and carbohydrates composition in ...
Modulation of gene expression by calreticulin binding to the glucocorticoid receptor
Calreticulin is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin has been reported to bind to the synthetic peptide …
2021 CRT-211 New Question - CRT-211 Certification Exam, Salesforce Certified Advanced Administrator Exam Latest Test...
Efficient CRT-211 New Question - Easy and Guaranteed CRT-211 Exam Success, We can ensure you that you will receive our CRT-211 practice exam materials within 5 to 10 minutes after payment, this marks the fastest delivery speed in this field, Salesforce CRT-211 New Question Chances favor the prepared mind, Passing a CRT-211 exam to get a certificate will help you to look for a better job and get a higher salary, If you are the first time to prepare the CRT-211 exam, it is better to choose a type of good study materials.
In vitro Assays for the Detection of Calreticulin Exposure, ATP and HMGB1 Release upon Cell Death -BIO-PROTOCOL
Accumulating evidence is revealing the essential role of immune system in cancer treatment. Certain chemotherapeutic drugs can potently induce the release of cell death associated molecular patterns (CDAMPs), which accompanies cancer cell demise. CDAMPs can engage corresponding receptors on immune cells and stimulate immune responses to achieve long-term tumor control (Ma et al., 2013; Ma et al., 2014; Yang et al., 2015). Among reported CDAMPs, calreticulin (CALR), ATP and HMGB1 are well known for their immune-stimulatory effect. Here we describe the assays that we applied to measure cell death and these CDAMPs. Briefly, cell death can be analyzed by co-staining of 4,6-diamidino-2-phenylindole (DAPI) with 3,3-Dihexyloxacarbocyanine Iodide [DiOC6(3)] or Annexin V. CALR exposure on the cell membrane can be detected by flow cytometry. ATP and HMGB1 release can be quantified by luminescence assay and ELISA assay respectively.
Evolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders<...
TY - JOUR. T1 - Evolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders. AU - Kotian, Vignesh. AU - Sarmah, Deepaneeta. AU - Kaur, Harpreet. AU - Kesharwani, Radhika. AU - Verma, Geetesh. AU - Mounica, Leela. AU - Veeresh, Pabbala. AU - Kalia, Kiran. AU - Borah, Anupom. AU - Wang, Xin. AU - Dave, Kunjan R. AU - Yavagal, Dileep R. AU - Bhattacharya, Pallab. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its housekeeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis, it performs a variety of noncanonical roles, mostly in CNS development. In the past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons. Many neurological disorders that differ in their etiology are commonly associated with aberrant levels of ...
Regulation of the Calreticulin Gene by GATA6 and Evi-1 Transcription Factors †
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RCSB PDB - 5LK5: Crystal structure of the globular domain of human calreticulin mutant D71K
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Calreticulin - CFGparadigms
This family of GBPs is widespread in evolution and plays a key role in ER quality control,ref name=Ellgaard 2003a,Ellgaard, L. and Frickel, E. M. Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding. Cell Biochem Biophys 39, 223-247 (2003),/ref,,ref name=Jorgensen 2003,Jorgensen, M. M., Bross, P. and Gregersen, N. Protein quality control in the endoplasmic reticulum. APMIS Suppl 86-91 (2003),/ref,,ref name=Ellgaard 2003,Ellgaard, L. and Helenius, A. Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4, 181-191 (2003),/ref,,ref name=Helenius 2004,Helenius, A. and Aebi, M. Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73, 1019-1049 (2004),/ref,,ref,Molinari, M., Eriksson, K. K., Calanca, V., Galli, C., Cresswell, P., Michalak, M. and Helenius, A. Contrasting functions of calreticulin and calnexin in glycoprotein folding and ER quality control. Mol Cell 13, 125-135 (2004),/ref,,ref,Deprez, P., Gautschi, M. and Helenius, A. More ...
Antibody to calreticulin
Does anyone have an antibody to human calreticulin that they can let us have for work on rheumatoid arthritis? Thanks Frank -- Frank C Hay Division of Immunology St Georges Hospital Medical School London SW17 0RE, UK Tel: 0181 767 5751 Fax: 0181 725 3549 email: frank at rabbits.demon.co.uk ...
Sourcing the immune system to induce immunogenic cell death in Kras-colorectal cancer cells | British Journal of Cancer
Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations. Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts. We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Kras-mut/TP53-mut colorectal cancer cells the 15 kDa βGBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a
Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death. - Immunology
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called damage-associated molecular patterns (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of
Crizotinib-induced immunogenic cell death in non-small cell lung cancer - HTE Program
Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional ...
Calreticulin Summary Report | CureHunter
Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
Zinc-Dependent Homomultimerization of Mutant Calreticulin Is Required for MPN Pathogenesis | Blood | American Society of...
Recurrent mutations in the ER chaperone calreticulin (CALR) are found in ~30% of MPNs. All known CALR mutations result in a +1-frameshift of the CALR reading fr
Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity<...
TY - JOUR. T1 - Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity. AU - Kinoshita, G.. AU - Keech, C. L.. AU - Sontheimer, R. D.. AU - Purcell, A.. AU - McCluskey, J.. AU - Gordon, T. P.. PY - 1998/2/9. Y1 - 1998/2/9. N2 - Calreticulin (CR) is widely recognized as a new human autoantigen but there are conflicting data concerning its relationship with the Ro(SS-A) ribonucleoprotein (RNP). Recent evidence suggests that CR binds to 52 kDaRo (Ro52) by a protein/protein interaction and binds to hY RNA and rubella virus RNA. Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice. These findings support a physical association of these polypeptides in Ro/La complexes. To test the hypothesis that CR is physically associated with Ro52 and/or Ro60 we examined the sera of Ro52-, Ro60- ...
Most Popular CRT-251 Testing Technology - Free Salesforce CRT-251 Test Braindump - CRT-251 Exam Materials Online at Actual...
Actual Exams Sales Cloud Consultant training service - Salesforce CRT-251 online test materials with real CRT-251 practice exam questions.
Immunogenic tumor cell death induced by chemotherapy in patients with breast cancer and esophageal squamous cell carcinoma
The present study contains novel findings supporting the concept that ICD can be induced by chemotherapy alone in patients with breast cancer and ESCC. Firstly, both HMGB1 and calreticulin expression were significantly upregulated after NAC. Secondly, chemotherapeutic drugs induced the upregulation of HMGB1 and calreticulin in several tested breast cancer cell lines.. We and others have recently reported that danger signals from dying cells following treatment with radiotherapy or certain chemotherapeutic drugs, such as anthracyclines and oxaliplatin, can induce Toll-like receptor (TLR)-dependent, antigen-specific T-cell immunity (22,23). Additional therapeutic modalities shown to induce ICD include oncolytic virus therapy (24-26) and photodynamic therapy (27,28). Furthermore, among various danger signals released from dying cells in a tumor-bearing mouse model, HMGB1, but not other known TLR4 ligands, could be a mandatory factor to induce tumor antigen-specific T-cell immunity (22,23). ...
Plus it
The present study contains novel findings to support the concept of immunogenic cell death induced by chemoradiotherapy in patients with ESCC. First, tumor antigen-specific T-cell responses were confirmed in 6 (38%) of 16 patients with ESCC following chemoradiotherapy. Second, the serum level of HMGB1 following chemoradiation in the patients with antigen-specific T-cell responses was significantly elevated in comparison to that in the patients without antigen-specific T-cell responses. Third, upregulation of HMGB1 within tumor microenvironments was significantly related to preoperative chemoradiotherapy and the degree of HMGB1 positively correlated with patients survival. Fourth, both irradiation and chemodrugs could induce upregulation of HMGB1 and calreticulin on ESCC cell lines in vitro. Finally, HMGB1 was able to induce maturation of DCs in an in vitro culture system.. In general, chemoradiotherapy is thought to induce an immunosuppressive state in both T-cell and natural killer-cell ...
CALRETICULIN workshop
Dear All Please read attached document for details of 4th international CALRETICULIN workshop to be held at Oxford University in April 2000 If you have problems opening the attachment or are worried about viruses look at our homepage on:- http://www.uwcm.ac.uk/uwcm/mb/crt2000.html Yours sincerely, Paul Eggleton. Dept Biochemistry. University of Oxford. UK ...
Researchers show how mutant CALR protein triggers cancer
Researchers at Juntendo University report in the journal Leukemia how mutants of the protein calreticulin lead to molecular mechanisms triggering myeloproliferative neoplasms, which can cause cancer. The findings may lead to the development of novel therapies for certain types of blood cancer.
Plus it
Two key factors that mediate high-glucose-induced downregulation of the glucose transport system in bovine aortic endothelial cells and in the human-derived EA.hy926 cells have been identified: the lipid peroxidation product 4-HDDE and its cognate nuclear receptor PPARδ. The latter increases the expression of the protein calreticulin that was shown before to destabilize GLUT-1 mRNA (13).. The augmented production of 4-HDDE results from high-glucose-induced 12-LO expression and activity and glucose-derived ROS. The mechanism responsible for the increased expression of 12-LO is not yet known. Numerous studies have proven that hyperglycemia promotes the generation of ROS (3,7). We showed before an augmented production of ROS in bovine aortic endothelial cell primary cultures under high-glucose conditions (28). Two observations confirm the role of ROS in the generation of 4-HDDE from 12-LO metabolites. First, the inhibition of 12-LO activity with baicalein significantly reduced 4-HDDE secretion ...
Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology. | Sotio
The term immunogenic cell death (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the ...
Oxygen and oxaliplatin-loaded nanoparticles combined with photo-sonodynamic inducing enhanced immunogenic cell death in...
Immunotherapy by stimulating the host immune system has been a promising therapeutic strategy for advanced ovarian cancer. Here we describe a treatment strategy that combines chemotherapy and photo-sonodynamic therapy (PSDT) to induce systemic antitumor immunity. We have successfully fabricated phase-changeable core-shell nanoparticles (OIX_NPs), which carry oxygen in the core and the photosensitizer indocyanine green (ICG)/oxaliplatin (OXP) in the shell for our combination therapy.
Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell-driven rejection of high-grade glioma ...
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Immunogenic cell death in cancer therapy. - PubMed - NCBI
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Differential association of calreticulin type 1 and type 2 mutations with myelofibrosis and essential thrombocytemia: relevance...
Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., Avezov E., Li J., Kollmann K., Kent D.G., Aziz A., Godfrey A.L., Hinton J., Martincorena I., Van Loo P., Jones A.V., Guglielmelli P., Tarpey P., Harding H.P., Fitzpatrick J.D., Goudie C.T., Ortmann C.A., Loughran S.J., Raine K., Jones D.R., Butler A.P., Teague J.W., OMeara S., McLaren S., Bianchi M., Silber Y., Dimitropoulou D., Bloxham D., Mudie L., Maddison M., Robinson B., Keohane C., Maclean C., Hill K., Orchard K., Tauro S., Du M.-Q., Greaves M., Bowen D., Huntly B.J.P., Harrison C.N., Cross N.C.P., Ron D., Vannucchi A.M., Papaemmanuil E., Campbell P.J., Green A.R., Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2, 10.1056/nejmoa1312542 ...
Calr - Calreticulin - Mus musculus (Mouse) - Calr gene & protein
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
JCI - Usage information: Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis
Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores. Furthermore, human carriers of the 9p21 risk allele had reduced expression of CDKN2B in atherosclerotic plaques, which was associated with impaired expression of calreticulin, a ligand required for activation of engulfment receptors on phagocytic cells. As a result of decreased calreticulin, CDKN2B-deficient apoptotic bodies were resistant to efferocytosis and not efficiently cleared by neighboring macrophages. These ...
KAKEN - Research Projects | Overexpression of calreticulin modulates protein kinase B/Akt signaling to promote apoptosis during...
Principal Investigator:TODA Genji, Project Period (FY):2001 - 2002, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Circulatory organs internal medicine
calreticulin 3 (mouse)
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
Targeted therapy and radiation drug combinations ( - University of Manchester)
Lead: Tim Illidge. Radiation treatment (RT) is a highly effective anti-cancer treatment that is delivered to over 50% of all cancer patients and 40% of those cured of their disease.. In order to further improve cancer outcomes using RT, an increased understanding of what determines effective RT-induced anti-tumour responses and how best to combine RT with others treatments is required.. Our research programme evaluates the contribution of RT-induced immunogenic cell death to the induction of tumour-specific immune responses (Project 1); determines how best to integrate RT with immunomodulatory agents to augment such responses and enhance therapeutic outcome (Project 2); and investigates how combination with RT and immune modulation can be utilised to increase the efficacy and durability of anti-CD20 mAb therapy in B- cell lymphomas (Project 3).. The pre-clinical experimental programme runs in parallel with early phase clinical trials to form a cohesive and overlapping programme of work that aims ...
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Purpose: To characterize the ability of PT-112 to induce immunogenic cell death (ICD) in vitro and in vivo. Background: PT-112 is a novel chemical entity consisting of a platinum core conjugated to a pyrophosphate and diaminocyclohexane groups. In vitro studies demonstrated that PT-112 has both cytostatic and cytotoxic effects on human cancer cells, two effects that are seen in the absence of robust binding to nuclear DNA. Accordingly, PT-112 potency is largely unaffected by functional DNA repair pathways, suggesting that PT-112 operates with mechanisms that differ from conventional DNA-damaging chemotherapies. PT-112 is currently under phase I/II clinical development in patients with solid tumors and hematologic malignancies, both as monotherapy and in combination with a PD-L1 inhibitor. Interim reports have established encouraging tolerability and signals of single-agent anticancer activity. Previous work with human colorectal cancer HCT-116 cells demonstrated that PT-112 causes the release of ...
Addgene: mEmerald-Calreticulin-C-10
Plasmid mEmerald-Calreticulin-C-10 from Dr. Michael Davidsons lab contains the insert Calreticulin. This plasmid is available through Addgene.
CALR antibody (ARP30114 P050) | Tested with: Human HepG2 cells
CALR antibody - C-terminal region (ARP30114_P050) | Application: WB | CALR is strongly supported by BioGPS gene expression data to be expressed in Human HepG2 cells | Alias: RO; CRT; SSA; cC1qR
Gene Variant Detail
CALR D45Y lies within the N-domain region of the Calr protein (UniProt.org). D45Y has been identified in the scientific literature (PMID: 29218307) but has not been biochemically characterized and therefore, its effect on Calr protein function is unknown (PubMed, Feb 2020 ...
Effects of prenatal glucocorticoid exposure on cardiac calreticulin and calsequestrin protein expression during early...
Overexpression of the conserved Ca2+-binding proteins calreticulin and calsequestrin impairs cardiac function, leading to premature death. Calreticulin is vital for embryonic development, but also impairs glucocorticoid action. Glucocorticoid overexposure during late fetal life causes intra-uterine growth retardation and programmed hypertension in adulthood. To determine whether intra-uterine growth retardation or programmed hypertension was associated with altered calreticulin or calsequestrin expression, effects of prenatal glucocorticoid overexposure (maternal dexamethasone treatment on days 15-21 of pregnancy) were examined during fetal life and postnatal development until adulthood (24 weeks). Dexamethasone (100 or 200μg/kg of maternal body weight) was administered via osmotic pump. Calreticulin was detected as a 55kDa band and calsequestrin as 55 and 63kDa bands in 21 day fetal hearts. Only the 55kDa calsequestrin band was detected postnatally. Prenatal glucocorticoid overexposure at the ...
Synthetic immunogenic cell death mediated by intracellular delivery of STING agonist nanoshells enhances anti-cancer chemo...
Many favorable anti-cancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which activates antigen presenting cells to prime anti-cancer adaptive immunity. We describe a strategy to synthetically induce ICD by delivering the agonist of stimulator of interferon genes (STING), 23′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris, by a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics adopted for cancer treatment and enables co-localization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and development of anticancer adaptive immunity. In three mouse tumor models with distinctive chemotherapeutic treatments, sICD enhances therapeutic efficacy ...
Immunogenic cell death of dendritic cells following modified vaccinia virus Ankara infection enhances CD8(+) T cell...
Immunogenic cell death (ICD) is associated with the emission of so-called damage-associated molecular patterns (DAMPs) which trigger the immune response against dead-cell associated antigens. The secretion of the DAMP, adenosine triphosphate (ATP) has been shown to be autophagy-dependent. Here, we demonstrate that Modified Vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, induces both cell death and autophagy in murine bone marrow-derived dendritic cells (BMDCs), which in turn confer the (cross-)priming of OVA-specific cytotoxic T cells (OT-I cells). Additionally, we show that MVA infection leads to increased extracellular ATP (eATP) as well as intracellular ATP (iATP) levels, with the latter being influenced by the autophagy. Furthermore, we show that the increased eATP supports the proliferation of OT-I cells and inhibition of the P2RX7 receptors results in an abrogation of the proliferation. These data reveal novel mechanisms on how MVA enhances adaptive immunity in ...
Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection? | BMC Cancer | Full...
We have proposed that rTcCRT [13, 14] provides an important at least partial explanation of why T. cruzi experimental infection or the inoculation of parasite extracts exerts toxic effects on different tumor types, mammary adenocarcinoma among them (reviewed in [2]).. We have described a 45 kDa T. cruzi, highly pleiotropic chaperone protein, TcCRT [13]. rTcCRT [13] is antiangiogenic because it inhibits ECs proliferation, migration and morphogenesis, in several in vitro, ex vivo and in vivo assays, in 3 species, H. s. sapiens included [9, 16, 17]. Furthermore, in vivo, rTcCRT inhibits the growth of an experimental mammary adenocarcinoma, when inoculated in an area near the tumor. This effect is more potent than the one elicited by its rHuCRT counterpart [9]. However, the proposal that T.cruzi infection has an antitumor effect mediated by its nTcCRT, needs a formal demonstration, as justified in the Introduction section. This important question was addressed herein. In order to causally implicate ...
An Immunosurveillance Mechanism Controls Cancer Cell Ploidy | Science
The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as hyperploid cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...
An Immunosurveillance Mechanism Controls Cancer Cell Ploidy | Science
The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as hyperploid cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...
Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death -...
High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling immunogenic chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4+ and CD8+ T cell-dependent protective immunity in vivo. Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2α phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation. Non-phosphorylatable eIF2α, depletion of PERK, caspase-2 or -8 compromised calreticulin exposure by cancer cells succumbing to HHP but could not inhibit death. Interestingly, the phagocytosis of HHP-treated malignant cells by dendritic cells was suppressed by the knockdown of caspase-2 in the former. Thus, caspase-2 mediates a key function in the interaction between dying cancer cells and antigen presenting cells. Our results indicate that the ROS→PERK→eIF2α
Endoplasmic Reticulum and cis-Golgi Localization of Human T-Lymphotropic Virus Type 1 p12I: Association with Calreticulin and...
In this study, we determined the subcellular accumulation of HTLV-1 p12I to further define the possible function for this protein in viral infection. We demonstrate that p12I is retained as a membrane-associated protein and is expressed predominantly in the ER and cis-Golgi apparatus. Two regions of the protein containing predicted transmembrane domains are independently responsible for this pattern of localization. Importantly, we are the first to identify the interaction of p12I with both calreticulin and calnexin in the ER, suggesting a possible function of the viral protein in calcium-mediated cell signaling leading to host cell activation. These findings are consistent with our previous studies that demonstrated a requirement for HTLV-1 p12I in viral infectivity both in a rabbit model of infection (12), in primary lymphocytes in vitro (1), and in calcium-dependent nuclear factor of activated T cells-mediated transcription (B. Albrecht et al., unpublished data).. HTLV-1 p12I is highly ...
Three Novel Calreticulin Mutations in Two Turkish Patients [Turk J Hematol]
Veysel Sabri Han er, H seyin Tokg z, Serkan G ven , mran al kan, Murat B y kdo an. Three Novel Calreticulin Mutations in Two Turkish Patients. Turk J Hematol. 2017; 34(4): 360- ...
A 4-trifluoromethyl analogue of celecoxib inhibits arthritis by suppressing innate immune cell activation | Arthritis Research ...
In the present study we demonstrate, using arthritis models, that TFM-C, a celecoxib analogue with 205-fold lower COX-2-inhibitory activity, inhibits autoimmune disease. TFM-C differs from celecoxib by the substitution of the 4-methyl group by a trifluoromethyl group. This substitution drastically increases the IC50s for inhibition of COX1 (15 μM to ,100 μM for celecoxib and TFM-C, respectively) and COX2 (0.04 μM to 8.2 μM, respectively), but does not affect the apoptotic index measured in PC3 prostate cancer cells, indicating independence between structural requirements for COX-2 inhibition and apoptosis induction [36]. Celecoxib perturbs intracellular calcium by blocking ER Ca2+ ATPases, and this activity is shared with TFM-C [23, 37]. In a HEK293 recombinant cell system, this Ca2+ perturbation is associated with inhibition of secretion and altered intracellular interaction of IL-12 polypeptide chains with the ER chaperones calreticulin and ERp44, and results in the interception of IL-12 ...
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47 | Science...
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buy AZD4547 - casein kinases mediate the phosphorylatable protein pp49
Platinum-based chemotherapy produced a paradigm shift in the treating different cancers initially; nevertheless, the success of the agents may reach the top as researchers have got tried different mixture regimes in various trials without having major differences in the end results. is still significant research required to accomplish full understanding of these resistance mechanisms to overcome the ineffectiveness or toxicities of platinum compounds. It seems affordable in the current perspective when standard chemotherapeutic brokers exhibited immunogenic cell death and they are currently in use with monoclonal antibodies to revisit the platinum brokers pharmacology. This may discover new basis for combination chemotherapy with monoclonal antibodies which may buy AZD4547 improve the current malignancy treatments by opening new vistas for newer buy AZD4547 combination regimes with less toxicity and better efficacy. In this article we review the pharmacologies of both cisplatin and oxaliplatin ...
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New treatments for triple-negative breast cancer (TNBC) are urgently needed. Despite there being little evidence of clinical activity as single-agent therapies, we show that dual blockade of PI3Kα and CDK4/6 is synergistically effective against multiple RB1-wild-type TNBC models. Combined PI3Kα and CDK4/6 inhibition significantly increased apoptosis, cell-cycle arrest, and tumor immunogenicity and generated immunogenic cell death in human TNBC cell lines. Combination treatment also significantly improved disease control in human xenograft models compared with either monotherapy. Combined PI3Kα and CDK4/6 inhibition significantly increased tumor-infiltrating T-cell activation and cytotoxicity and decreased the frequency of immunosuppressive myeloid-derived suppressor cells in a syngeneic TNBC mouse model. Notably, combined PI3Kα and CDK4/6 inhibition, along with inhibition of immune checkpoints PD-1 and CTLA-4, induced complete and durable regressions (,1 year) of established TNBC tumors in ...
ICD Components | Nano Publications
NBTXR3 exposed to irradiation enhanced cancer cells destruction and immunogenic cell death compared to irradiation alone, suggesting a strong potential for transforming tumor into an effective in situ vaccine. This may contribute to transform cold tumor into hot tumor and effectively be combined with most of the immunotherapeutic agents across oncology. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.. Continuer la lecture…. ...
UNC119B Gene - GeneCards | U119B Protein | U119B Antibody
Complete information for UNC119B gene (Protein Coding), Unc-119 Lipid Binding Chaperone B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium