Abstract
Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.
Keywords:
Apoptosis; CSL-dependent Notch; CSL-independent Notch; Cell; mTORC.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Apoptosis / genetics*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Carcinogenesis / genetics*
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Carcinogenesis / metabolism
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Carcinogenesis / pathology
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Cell Proliferation
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Gene Expression Regulation, Neoplastic*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics*
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
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Neoplasms / genetics*
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Neoplasms / metabolism
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Neoplasms / pathology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, Notch1 / genetics*
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Receptor, Notch1 / metabolism
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Signal Transduction
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Homeodomain Proteins
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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NOTCH1 protein, human
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Protein Isoforms
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RBPJ protein, human
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Receptor, Notch1
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Transcription Factor HES-1
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HES1 protein, human
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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PTEN Phosphohydrolase
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PTEN protein, human