RESUMO
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 31.1 with a constitutively active, intracellular form of human Notch1 (Notch1-ICT). NYC cells represent mature activated B cells that can be induced to undergo apoptosis by crosslinking of the B-cell receptor (BCR). In contrast to investigations in immature chicken B-cell lines, transduced Notch1-ICT did not affect cell cycle progression, cell growth or surface IgM levels in NYC cells and resulted only in a slight induction of apoptosis. However, BCR-crosslinking enhanced apoptosis, but did not influence cell cycle progression in Notch1-ICT-positive NYC cells. These data imply a distinct function of Notch1 in mature murine B-cells as compared to immature chicken B cells and provide further evidence for Notch1's involvement in B-cell differentiation and development.
Assuntos
Apoptose/imunologia , Linfócitos B/metabolismo , Imunoglobulina M/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição , Animais , Apoptose/genética , Linfócitos B/imunologia , Ciclo Celular/genética , Ciclo Celular/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Galinhas , Hematopoese/genética , Hematopoese/imunologia , Camundongos , Receptor Notch1 , Receptores de Superfície Celular/genética , Especificidade da Espécie , Transdução Genética , Regulação para Cima/genética , Regulação para Cima/imunologiaRESUMO
The Notch receptor protein was originally identified in Drosophila and is known to mediate cell to cell communication and influence cell fate decisions. Members of this family have been isolated from invertebrates as well as vertebrates. We isolated mouse Notch-1 in a yeast two-hybrid screen with Nur77, which is a protein that has been shown previously to be required for apoptosis in T cell lines. The data presented below indicate that Notch-1 expression provides significant protection to T cell lines from TCR-mediated apoptosis. These data demonstrate a new antiapoptotic role for Notch-1, providing evidence that, in addition to regulating cell fate decisions, Notch-1 can play a critical role in controlling levels of cell death in T cells.
Assuntos
Apoptose/imunologia , Proteínas de Membrana/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Receptores de Superfície Celular , Animais , Morte Celular/genética , Morte Celular/imunologia , Linhagem Celular , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Humanos , Células Híbridas , Linfoma de Células T , Camundongos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Receptor Notch1 , Receptores Citoplasmáticos e Nucleares , Receptores de Esteroides , Retroviridae/genética , Saccharomyces cerevisiae/genética , Linfócitos T/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Células Tumorais CultivadasRESUMO
Apoptosis, one of the best-studied forms of programmed cell death processes, plays an important role during the development and life-cycle of most multicellular organisms. The mechanisms underlying the initiation and manifestation of apoptotic cell death are the focus of the most recent cell death research. Generally, it is believed that cells are eliminated via a highly ordered and controlled program. This program might consist of the successive activation of unique apoptosis-specific genes, which are solely involved in the regulation of the programmed cell death. However, more and more evidence is accumulating that novel genes are not activated or induced during apoptosis, but rather many well-known genes previously described for their roles in processes such as proliferation and differentiation and belonging, for example, to the protein families of immediate-early genes and transcription factors become activated. The death-specific feature is achieved thereby by the extent, combination, and specific timing of gene expression. The involvement of the three different transcription factors glucocorticoid receptor (GR), nur77, and activator protein 1 (AP-1) in such a scenario is the focus of this review.
