Transducing signals of life and death
Current Opinion in Cell BiologyPublished 1 April 1997
Junying Yuan
Citations308
SJR quartileQ1
SJR score2.78
SNIP1.19
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The molecules that form signaling complexes with the cytoplasmic domains of tumor necrosis factor receptors (TNF-Rs) and CD95 have been identified recently and interact with the members of both the TNF-R associated factor family and the inhibitor of apoptosis protein family; these interactions lead to cell survival.
Abstract
The molecules that form signaling complexes with the cytoplasmic domains of tumor necrosis factor (TNF) receptors (TNF-Rs) and CD95 have been identified recently. The death-signaling pathways induced by TNF-R1 and CD95 involve a group of death domain containing proteins, including caspase-8, a member of the interleukin-1beta-converting enzyme family. TNF-R1 and TNF-R2 also interact with the members of both the TNF-R associated factor family and the inhibitor of apoptosis protein family; these interactions lead to cell survival.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
ScienceAn Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
3,075 Citations1996Amer A. Beg, David Baltimore
Treatment of RelA-deficient (RelA-/-) mouse fibroblasts and macrophages with TNF-alpha resulted in a significant reduction in viability, whereas RelA+/+ cells were unaffected, demonstrating that the presence ofrelA is required for protection from TNF.
CellFLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex
3,060 Citations1996Marta Muzio, Arul M. Chinnaiyan +12 more
This work utilized nano-electrospray tandem mass spectrometry to identify CAP3 and CAP4, components of the CD95 (Fas/APO-1) death-inducing signaling complex, and found a novel 55 kDa protein, designated FLICE, which has homology to both FADD and the ICE/CED-3 family of cysteine proteases.
CellThe polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis
2,787 Citations1991Naoto Itoh, Shin Yonehara +7 more
Complementary DNAs encoding the cell surface antigen Fas were isolated from a cDNA library of human T cell lymphoma KT-3 cells and revealed that the molecule coding for the Fas antigen determinant is a 319 amino acid polypeptide with a single transmembrane domain.
ScienceTNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB
2,637 Citations1996Cun-Yu Wang, Marty W. Mayo +1 more
The activation of the transcription factor nuclear factor-kappa B by tumor necrosis factor, ionizing radiation, or daunorubicin, was found to protect from cell killing, providing a mechanism of cellular resistance to killing by some apoptotic reagents.
ScienceSuppression of TNF-α-Induced Apoptosis by NF-κB
2,608 Citations1996Daniel J. Van Antwerp, Séamus J. Martin +3 more
The sensitivity and kinetics of TNF-α-induced apoptosis are shown to be enhanced in a number of cell types expressing a dominant-negative IκB α (IκBαM).
CellFADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis
2,424 Citations1995Arul M. Chinnaiyan, Karen O’Rourke +2 more
Findings suggest that FADD may play an important role in the proximal signal transduction of Fas, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8.
CellInvolvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death
2,301 Citations1996Mark Boldin, Tanya Goncharov +2 more
This work cloned a novel protein, MACH, that binds to MORT1, and suggests that MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascades.
The EMBO JournalCytotoxicity‐dependent APO‐1 (Fas/CD95)‐associated proteins form a death‐inducing signaling complex (DISC) with the receptor.
2,149 Citations1995Frank Kischkel, Stefan Hellbardt +5 more
The data suggest that in vivo CAP1–4 are the APO‐1 apoptosis‐transducing molecules.
CellThe TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation
2,007 Citations1995Hailing Hsu, Jessie Xiong +1 more
The discovery of a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death shows that the signaling pathways for TNF-induced cell death and NF-κB activation are distinct.
CellTRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways
1,999 Citations1996Hailing Hsu, Hong-Bing Shu +2 more
It is shown that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively, and these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
CellDissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-κB Activation Prevents Cell Death
1,949 Citations1996Zheng-gang Liu, Hailing Hsu +2 more
This work investigated how TNFR1 activates different effector functions; the protein kinase JNK, transcription factor NF-kappaB, and apoptosis, finding that the three responses are mediated through separate pathways.
NatureTRAF6 is a signal transducer for interleukin-1
1,305 Citations1996Zhaodan Cao, Jessie Xiong +3 more
The identification of a new TRAF family member, designated TRAF6, indicates that TRAF proteins may function as signal transducers for distinct receptor families and that TRAf6 participates in IL-1 signalling.
ImmunityTNF-Dependent Recruitment of the Protein Kinase RIP to the TNF Receptor-1 Signaling Complex
1,167 Citations1996Hailing Hsu, Jianing Huang +3 more
It is shown that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen, and is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process.
CellA novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor
1,059 Citations1994Mike Rothe, Suzy C. Wong +2 more
This analysis indicates that TNF receptor-associated factor 1 (TRAF1) and TRAF2 are associated with the cytoplasmic domain of TNF-R2 in a heterodimeric complex in which TRAF 2 contacts the receptor directly and TNF1 interacts with TNF
ScienceTRAF2-Mediated Activation of NF-κB by TNF Receptor 2 and CD40
1,053 Citations1995Mike Rothe, Vidya Sarma +2 more
A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40.
Journal of Biological ChemistryA Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain
993 Citations1995Mark Boldin, Eugene Varfolomeev +4 more
Induced expression of the cloned protein results in ligand-independent triggering of cytotoxicity, suggesting that it is involved in cell death induction by Fas/APO1.
CellRIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death
975 Citations1995Ben Z. Stanger, Philip Leder +3 more
Transient overexpression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis, and these properties indicate that RIP is a novel form of apoptotic-inducing protein.
Journal of Biological ChemistryA novel protein domain required for apoptosis. Mutational analysis of human Fas antigen
845 Citations1993Naoto Itoh, Shigekazu Nagata
A 68-amino acid portion of the signal-transducing domain significantly conserved in the Fas antigen as well as in the type I tumor necrosis factor receptor was considered to be the novel protein domain required for apoptotic signal transduction.
Proceedings of the National Academy of SciencesThe two different receptors for tumor necrosis factor mediate distinct cellular responses.
814 Citations1991Louis A. Tartaglia, R F Weber +4 more
Investigation of the individual roles of the murine type 1 and type 2 tumor necrosis factor (TNF) receptors suggest that TNF-R2 initiates signals for the proliferation of thymocytes and cytotoxicity and the induction of the protective activity, manganous superoxide dismutase.
SciencePrevention of Apoptosis by a Baculovirus Gene During Infection of Insect Cells
811 Citations1991Rollie J. Clem, Marcus Fechheimer +1 more
Apoptosis, a morphologically and biochemically defined type of programmed cell death commonly seen in vertebrates, was found to be initiated during baculovirus replication in insect cells and a specific viral gene product, p35, was identified as being responsible for blocking the apoptotic response.
Journal of Biological ChemistryFADD/MORT1 Is a Common Mediator of CD95 (Fas/APO-1) and Tumor Necrosis Factor Receptor-induced Apoptosis
774 Citations1996Arul M. Chinnaiyan, Clifford G. Tepper +7 more
This work reports that an N-terminal truncation of one of these candidate signal transducers, FADD/MORT1, abrogates CD95-induced apoptosis, ceramide generation, and activation of the cell death protease Yama/CPP32.
ScienceFAP-1: A Protein Tyrosine Phosphatase That Associates with Fas
687 Citations1995Takaaki Sato, Shinji Irie +2 more
Gene transfer-mediated elevations in FAP-1 partially abolished Fas-induced apoptosis in a T cell line, consistent with an inhibitory effect of Fap-1 on Fas signal transduction.
ScienceSignal Transduction by DR3, a Death Domain-Containing Receptor Related to TNFR-1 and CD95
653 Citations1996Arul M. Chinnaiyan, Karen O’Rourke +8 more
Another member of the TNFR family, death receptor 3 (DR3), was identified and was shown to induce both apoptosis and activation of nuclear factor κB, and likely plays a role in regulating lymphocyte homeostasis.
The EMBO JournalRIP mediates tumor necrosis factor receptor 1 activation of NF‐kappaB but not Fas/APO‐1‐initiated apoptosis.
550 Citations1996Adrian T. Ting, Felipe X. Pimentel‐Muiños +1 more
An analysis of cells reconstituted with mutant forms of RIP reveals similarities between the action of RIP and FADD/MORT‐1, a Fas‐associated death domain protein.
Proceedings of the National Academy of SciencesCloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors.
512 Citations1996Anthony G. Uren, M Pakusch +3 more
Results suggest that IAP proteins that inhibit apoptosis may do so by regulating signals required for activation of ICE-like proteases, as MIHB and MIHC were able to bind to the tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 in yeast two-hybrid assays.
ScienceInvolvement of CRAF1, a relative of TRAF, in CD40 signaling
455 Citations1995Genhong Cheng, Aileen M. Cleary +4 more
A yeast two-hybrid screen identified a gene, CRAF1, encoding a protein that interacts directly with the CD40 cytoplasmic tail through a region of similarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associated factors.
Proceedings of the National Academy of SciencesTRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling.
345 Citations1996Takafumi Ishida, Taiki Tojo +6 more
The results suggest that TRAF5 and TRAF3 could be involved in both common and distinct signaling pathways emanating from CD40, which play crucial roles in B-cell function.
NatureA death-domain-containing receptor that mediates apoptosis
336 Citations1996Jeremy Kitson, Thomas Raven +7 more
The isolation of a 54K receptor that is a new member of the TNFR superfamily is reported, using the death domain of TNFR1 in a yeast two-hybrid system, and this protein, WSL-1, is most similar toTNFR1 itself, particularly in the death-domain region.
Journal of Biological ChemistryPresence of a New Conserved Domain in CART1, a Novel Member of the Tumor Necrosis Factor Receptor-associated Protein Family, Which Is Expressed in Breast Carcinoma
228 Citations1995Catherine H. Régnier, Catherine Tomasetto +5 more
Observed association of RING, CART, and TRAF domains was observed in the human CD40-binding protein and in the mouse tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), both involved in signal transduction mediated by the TNF receptor family.
Current Opinion in Cell BiologyMolecular control of life and death
96 Citations1995Junying Yuan
Findings reveal key molecules that control life and death decisions in vertebrates.
PubMedCD95 (APO-1/Fas)-associating signalling proteins.
75 Citations1996Marcus E. Peter, Frank Kischkel +4 more
This review focuses on recent advances in the understanding of the proximal signal transduction mechanism of CD95, the NGF/TNF-receptor superfamily, members of which need to be trimerized by specific protein ligands in order to generate a signal.