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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-2-15
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pubmed:abstractText |
Excessive signaling via the Notch1 receptor inhibits apoptosis in T lymphocytes. Since several antiapoptotic proteins are cleaved by caspases during cell death, we investigated whether Notch1 was a caspase substrate. Results demonstrate that the intracellular domain of Notch1 (NICD) is cleaved into six fragments during apoptosis in Jurkat cells or peripheral T lymphocytes. Notch1 cleavage is prevented by the caspase inhibitors DEVD-fmk and VEID-fmk or by Bcl-2 expression. Caspase-3 and caspase-6 cleave the NICD into six fragments using sites located within the NF-kappaB binding domain, the ankyrin repeats and the transactivation domain. Notch1 cleavage correlates with the loss of HES-1 expression in apoptotic T cells. Notch1 fragments cannot inhibit activation-induced cell death in a T-cell hybridoma, confirming the abrogation of Notch1 antiapoptotic activity by caspases. The ability of the NICD but not the fragments to antagonize Nur77 activity supports a role for this factor in Notch1 antiapoptotic function.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HES1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NR4A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Steroid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
243-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15650752-Amino Acid Sequence,
pubmed-meshheading:15650752-Apoptosis,
pubmed-meshheading:15650752-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:15650752-Caspase 3,
pubmed-meshheading:15650752-Caspase 6,
pubmed-meshheading:15650752-Caspases,
pubmed-meshheading:15650752-Cell Line,
pubmed-meshheading:15650752-Cysteine Proteinase Inhibitors,
pubmed-meshheading:15650752-DNA-Binding Proteins,
pubmed-meshheading:15650752-Homeodomain Proteins,
pubmed-meshheading:15650752-Humans,
pubmed-meshheading:15650752-Hybridomas,
pubmed-meshheading:15650752-Molecular Sequence Data,
pubmed-meshheading:15650752-NF-kappa B,
pubmed-meshheading:15650752-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:15650752-Protein Structure, Tertiary,
pubmed-meshheading:15650752-Receptor, Notch1,
pubmed-meshheading:15650752-Receptors, Cell Surface,
pubmed-meshheading:15650752-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15650752-Receptors, Steroid,
pubmed-meshheading:15650752-Signal Transduction,
pubmed-meshheading:15650752-T-Lymphocytes,
pubmed-meshheading:15650752-Transcription Factor RelA,
pubmed-meshheading:15650752-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Notch1 antiapoptotic activity is abrogated by caspase cleavage in dying T lymphocytes.
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pubmed:affiliation |
Laboratoire d'Immunologie, CR-CHUM, campus St-Luc, Pavillon Edouard-Asselin, 264 Bd. René Lévesque E., Montréal, Québec, Canada H2X 1P1. luchino.cohen@umontreal.ca
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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