Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression

Romer, Simona; Saunders, Ute; Jäck, Hans‐Martin; Bm, Jehn

doi:10.1038/sj.cdd.4401253

Cited by 27 publications

(20 citation statements)

References 55 publications

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“…1C), an incubation time that results in maximal stabilization of BCR in DRM (5). We extended our study to the B cell lymphoma line NYC31.1, which is also apoptosis responsive upon BCR ligation (39). Intriguingly, the BCR was also exclusively detected outside DRM of NYC31.1 cells, even upon BCR engagement (Fig.…”

Section: Isolation Of Drm From B Cell Linesmentioning

confidence: 84%

“…This study analyzed the protein composition of DRM from B cell lines representing different developmental stages: 1) CH27 mature B cells, a cell line that does not undergo apoptosis after BCR stimulation (5); 2) WEHI231 cells, which represent the immature B cell stage and undergo apoptosis after BCR ligation (7); and 3) NYC31.1 cells, representing an activated B cell blast generated from mice prone to autoimmune disease (NZBϫNZW) (30), which also undergo apoptosis in response to BCR stimulation (39).…”

Section: Isolation Of Drm From B Cell Linesmentioning

confidence: 99%

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Lipid Rafts Associate with Intracellular B Cell Receptors and Exhibit a B Cell Stage-Specific Protein Composition

Mielenz

Vettermann

Hampel

et al. 2005

The Journal of Immunology

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Lipid rafts serve as platforms for BCR signal transduction. To better define the molecular basis of these membrane microdomains, we used two-dimensional gel electrophoresis and mass spectrometry to characterize lipid raft proteins from mature as well as immature B cell lines. Of 51 specific raft proteins, we identified a total of 18 proteins by peptide mass fingerprinting. Among them, we found vacuolar ATPase subunits α-1 and β-2, vimentin, γ-actin, mitofilin, and prohibitin. None of these has previously been reported in lipid rafts of B cells. The differential raft association of three proteins, including a novel potential signaling molecule designated swiprosin-1, correlated with the stage-specific sensitivity of B cells to BCR-induced apoptosis. In addition, MHC class II molecules were detected in lipid rafts of mature, but not immature B cells. This intriguing finding points to a role for lipid rafts in regulating Ag presentation during B cell maturation. Finally, a fraction of the BCR in the B cell line CH27 was constitutively present in lipid rafts. Surprisingly, this fraction was neither expressed at the cell surface nor fully O-glycosylated. Thus, we conclude that partitioning the BCR into lipid rafts occurs in the endoplasmic reticulum/cis-Golgi compartment and may represent a control mechanism for surface transport.

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Section: Isolation Of Drm From B Cell Linesmentioning

confidence: 84%

Section: Isolation Of Drm From B Cell Linesmentioning

confidence: 99%

Lipid Rafts Associate with Intracellular B Cell Receptors and Exhibit a B Cell Stage-Specific Protein Composition

Mielenz

Vettermann

Hampel

et al. 2005

The Journal of Immunology

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“…There are some investigations about involvement of Notch in B-cell malignancies. Notch signaling has been shown to inhibit proliferation and / or induce apoptosis in malignant B cells (30,31).…”

Section: Notch As a Tumor Suppressor In Hematologic Malignancesmentioning

confidence: 99%

Association between Notch signaling pathway and cancer

Lachej¹,

Didžiapetrienė²,

Kazbarienė³

et al. 2013

AML

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Background. The components of the Notch signaling pathway are important in maintaining the balance involved in cell proliferation, apoptosis and differentiation. Therefore, dysfunction of the Notch prevents differentiation, ultimately guiding undifferentiated cells toward malignant transformation. The aim of this article is to present recently published data concerning the role of the Notch signaling pathway components in development and prognosis of oncologic diseases, in occurrence of resistance to cytostatic agents and importance in creating of new cancer treatment approaches. Materials and methods. The Pubmed was the main source of looking for information for this article. Results. Recent investigations show that disorders of the Notch signaling pathway are associated with development of some human haematological and solid cancers. In different tissues and organs this active pathway can act as a tumor suppressor or an oncogene. Accordingly, the increased or decreased expression of its components is defined. Most of published data show that the increased expression of Notch pathway components correlates with a worse prognosis of cancer and a shorter survival. Recently, the Notch pathway has been reported to be involved in drug resistance. The modulation of the Notch signaling pathway could be helpful in treatment of some tumors with abnormal activity of this pathway’s components. Therefore changes in the expression of Notch components could become important predictive factors, helpful in selecting the proper treatment method. Conclusions. The results of recent studies are very important, since the detecting of the prognostic and predictive value of components of the Notch signaling pathway can allow creating new and improving already known methods of cancer diagnostic and treatment.

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“…14 Notch pathway has previously been shown to induce apoptosis in cell lines from different hematopoietic lineages most likely through the activation of its target gene hes1. [15][16][17] However, the overall data linking Notch and erythroid apoptosis is controversial. 18,19 In this work, we demonstrate that the Notch signaling pathway is a positive regulator of apoptosis in primitive erythropoiesis in the yolk sac but also in erythroid cells from adult bone marrow (BM).…”

Section: And Lai 2 )mentioning

confidence: 99%

The notch pathway positively regulates programmed cell death during erythroid differentiation

et al. 2007

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Programmed cell death plays an important role in erythropoiesis under physiological and pathological conditions. In this study, we show that the Notch/RBPjj signaling pathway induces erythroid apoptosis in different hematopoietic tissues, including yolk sac and bone marrow as well as in murine erythroleukemia cells. In RBPjj À/À yolk sacs, erythroid cells have a decreased rate of cell death that results in increased number of Ter119 þ cells. A similar effect is observed when Notch activity is abrogated by incubation with the c-secretase inhibitors, DAPT or L685,458. We demonstrate that incubation with Jagged1-expressing cells has a proapoptotic effect in erythroid cells from adult bone marrow that is prevented by blocking Notch activity. Finally, we show that the sole expression of the activated Notch1 protein is sufficient to induce apoptosis in hexametilene-bisacetamide-differentiating murine erythroleukemia cells. Together these results demonstrate that Notch regulates erythroid homeostasis by inducing apoptosis.

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Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression

Abstract: The transmembrane receptor Notch1 plays a crucial role in differentiation and apoptosis of hematopoietic cells. To investigate the influence of Notch1 on apoptosis and cell growth of mature murine B cells, we transduced the murine B-lymphoma line NYC 31

Cited by 27 publications

References 55 publications

Lipid Rafts Associate with Intracellular B Cell Receptors and Exhibit a B Cell Stage-Specific Protein Composition

Lipid Rafts Associate with Intracellular B Cell Receptors and Exhibit a B Cell Stage-Specific Protein Composition

Association between Notch signaling pathway and cancer

The notch pathway positively regulates programmed cell death during erythroid differentiation

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