Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes

Autor: Olivier Micheau, Jürg Tschopp
Přispěvatelé: Institute of Biochemistry, Université de Lausanne (UNIL)-BIL Biomedical Research Center, Université de Lausanne = University of Lausanne (UNIL)-BIL Biomedical Research Center, Micheau, Olivier
Rok vydání: 2003
Předmět:
MESH: Signal Transduction
Cytoplasm
MESH: CASP8 and FADD-Like Apoptosis Regulating Protein
Receptor complex
Fas-Associated Death Domain Protein
MESH: TNF Receptor-Associated Factor 1
CASP8 and FADD-Like Apoptosis Regulating Protein
MESH: NF-kappa B
Apoptosis
MESH: Caspase 9
MESH: Caspase 8
Receptors
Tumor Necrosis Factor

Jurkat Cells
0302 clinical medicine
Tumor Cells
Cultured

MESH: Jurkat Cells
MESH: Proteins
FADD
Caspase 8
0303 health sciences
Intracellular Signaling Peptides and Proteins
NF-kappa B
RNA-Binding Proteins
Signal transducing adaptor protein
MESH: Fas-Associated Death Domain Protein
respiratory system
Caspase Inhibitors
Caspase 9
MESH: Antigens
CD95

3. Good health
Cell biology
MESH: Cell Survival
Caspases
030220 oncology & carcinogenesis
Death-inducing signaling complex
Signal transduction
Signal Transduction
Transcriptional Activation
Cell Survival
Ripoptosome
MESH: Carrier Proteins
Biology
Models
Biological

General Biochemistry
Genetics and Molecular Biology

03 medical and health sciences
MESH: Intracellular Signaling Peptides and Proteins
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology

Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology

fas Receptor
MESH: Tumor Cells
Cultured

Transcription factor
Adaptor Proteins
Signal Transducing

MESH: Adaptor Proteins
Signal Transducing

030304 developmental biology
MESH: Humans
MESH: Caspases
Tumor Necrosis Factor-alpha
Biochemistry
Genetics and Molecular Biology(all)

MESH: Cytoplasm
MESH: Apoptosis
Cell Membrane
MESH: Models
Biological

Proteins
MESH: Receptors
Tumor Necrosis Factor

TNF Receptor-Associated Factor 1
TRADD
Nuclear Pore Complex Proteins
MESH: RNA-Binding Proteins
MESH: Tumor Necrosis Factor-alpha
biology.protein
MESH: Transcriptional Activation
Carrier Proteins
MESH: Nuclear Pore Complex Proteins
MESH: Cell Membrane
Zdroj: Cell
Cell, Elsevier, 2003, 114 (2), pp.181-90
ISSN: 0092-8674
1097-4172
DOI: 10.1016/s0092-8674(03)00521-x
Popis: Present adress of Olivier Micheau: INSERM U517, Faculties of Medicine and Pharmacy, 7 Bd Jeanne d'Arc, 21033 Dijon Cedex, France; International audience; Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
Databáze: OpenAIRE