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Project description:Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to "labeling" by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.
| S-EPMC6086865 | biostudies-literature
Project description:Loss of the p53-inducible LINC01021 in p53-proficient CRC cell lines results in increased sensitivity to DNA-damaging chemotherapeutics. Here, we comprehensively analyzed how LINC01021 affects the p53-induced transcriptional program. Using a CRISPR/Cas9-approach we deleted the p53 binding site in the LINC01021 promoter of SW480 colorectal cancer cells and subjected them to RNA-Seq analysis after activation of ectopic p53. RNA affinity purification followed by mass spectrometry was used identify proteins associated with LINC01021.
2024-05-10 | PXD050892 | Pride
Project description:Calreticulin is an abundant intracellular protein which is involved in a number of cellular functions. During cytomegalovirus infection, as well as inflammatory episodes in autoimmune disease, calreticulin can be released from cells and detected in the circulation, where it may act as an immunodominant autoantigen in diseases such as systemic lupus erythematosus. Calreticulin is known to bind to the molecules of innate immunity, such as C1q, the first subcomponent of complement. However, the functional implications of C1q-calreticulin interactions are unknown. In the present study we sought to investigate, in greater detail, the interaction between these two proteins following the release of calreticulin from neutrophils upon stimulation. In order to pinpoint the regions of interaction, recombinant calreticulin and its discrete domains (N-, P- and C-domains) were produced in Escherichia coli. Both the N- and P-domains of calreticulin were shown to bind to the globular head regions of C1q. Calreticulin also appeared to alter C1q-mediated immune functions. Binding of calreticulin to C1q inhibited haemolysis of IgM-sensitized erythrocytes. Both the N- and P-domains of calreticulin were found to contain sites involved in the inhibition of C1q-induced haemolysis. Full-length calreticulin, and its N- and P-domains, were also able to reduce the C1q-dependent binding of immune complexes to neutrophils. We conclude that calreticulin, once released from neutrophils during inflammation, may not only induce an antigenic reaction, but, under defined conditions, may also interfere with C1q-mediated inflammatory processes.
| S-EPMC1218224 | biostudies-other
Project description:Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accumulation at the site of inflammation can delay regenerative healing processes and can initiate pathological inflammatory processes. Thus, the efficient clearance of PMNs mediated by the induction of regulated cell death is a key process preventing the development of these pathological conditions. Myeloperoxidase (MPO), a highly abundant enzyme in PMN granules, primarily connected with PMN defense machinery, is suggested to play a role in PMN-regulated cell death. However, the contribution of MPO to the mechanisms of PMN cell death remains incompletely characterized. Herein, the process of the cell death of mouse PMNs induced by three different stimuli - phorbol 12-myristate 13-acetate (PMA), opsonized streptococcus (OST), and N-formyl-met-leu-phe (fMLP) - was investigated. MPO-deficient PMNs revealed a significantly decreased rate of cell death characterized by phosphatidylserine surface exposure and cell membrane permeabilization. An inhibitor of MPO activity, 4-aminobenzoic acid hydrazide, did not exhibit a significant effect on PMA-induced cell death compared to MPO deficiency. Interestingly, only the limited activation of markers related to apoptotic cell death was observed (e.g. caspase 8 activation, Bax expression) and they mostly did not correspond to phosphatidylserine surface exposure. Furthermore, a marker characterizing autophagy, cleavage of LC3 protein, as well as histone H3 citrullination and its surface expression was observed. Collectively, the data show the ability of MPO to modulate the life span of PMNs primarily through the potentiation of cell membrane permeabilization and phosphatidylserine surface exposure.
| S-EPMC8860816 | biostudies-literature
Project description:RNA-seq experiment of Calreticulin-mutated patients
| PRJNA655151 | ENA
Project description:BackgroundIdentifying novel tumor biomarkers to develop more effective diagnostic and therapeutic strategies for patients with ACC is urgently needed. The aim of the study was to compare the proteomic profiles between adrenocortical carcinomas (ACC) and normal adrenocortical tissues in order to identify novel potential biomarkers for ACC.MethodsThe protein samples from 12 ACC tissues and their paired adjacent normal adrenocortical tissues were profiled with two-dimensional electrophoresis; and differentially expressed proteins were identified by mass spectrometry. Expression patterns of three differently expressed proteins calreticulin, prohibitin and HSP60 in ACC, adrenocortical adenomas (ACA) and normal adrenocortical tissues were further validated by immunohistochemistry.ResultsIn our proteomic study, we identified 20 up-regulated and 9 down-regulated proteins in ACC tissues compared with paired normal controls. Most of the up-regulated proteins were focused in protein binding and oxidoreductase activity in Gene Ontology (GO) molecular function classification. By immunohistochemistry, two biomarkers calreticulin and prohibitin were validated to be overexpressed in ACC compared with adrenocortical adenomas (ACA) and normal tissues, but also calreticulin overexpression was significantly associated with tumor stages of ACC.ConclusionFor the first time, calreticulin and prohibitin were identified to be novel candidate biomarkers for ACC, and their roles during ACC carcinogenesis and clinical significance deserves further investigation.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1897372598927465.
| S-EPMC3640901 | biostudies-literature
Project description:RNA-sequencing analysis to identify genes regulated by MYCN in neuroblastoma cell line KCNR.
| PRJNA859871 | ENA
Project description:RNA-sequencing analysis to identify genes regulated by MYCN in rhabdomyosarcoma cell line RH4
| PRJNA859877 | ENA
Project description:RNA-seq in GR18 cell line to identify genes regulated by the Glucocorticoid Receptor
| PRJEB26484 | ENA
Project description:The first GSSM of V. vinifera was reconstructed (MODEL2408120001). Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases.
2024-09-02 | MODEL2408160001 | BioModels