FADD: a regulator of life and death

Tourneur, Léa; Chiocchia, Gilles

doi:10.1016/j.it.2010.05.005

Cited by 163 publications

(164 citation statements)

References 83 publications

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“…Within FADD, two essential domains designated the death domain (DD) and death effector domain (DED) are required for apoptotic transduction (35). A putative FADD protein containing the DD and DED domains has been identified in both Hydra and the A. digitifera proteome (aug_v2a.04795) (36,37).…”

Section: Discussionmentioning

confidence: 99%

Evolution of TNF-induced apoptosis reveals 550 My of functional conservation

Quistad

Stotland

Barott

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The Precambrian explosion led to the rapid appearance of most major animal phyla alive today. It has been argued that the complexity of life has steadily increased since that event. Here we challenge this hypothesis through the characterization of apoptosis in reef-building corals, representatives of some of the earliest animals. Bioinformatic analysis reveals that all of the major components of the death receptor pathway are present in coral with high-predicted structural conservation with Homo sapiens. The TNF receptor-ligand superfamilies (TNFRSF/TNFSF) are central mediators of the death receptor pathway, and the predicted proteome of Acropora digitifera contains more putative coral TNFRSF members than any organism described thus far, including humans. This high abundance of TNFRSF members, as well as the predicted structural conservation of other death receptor signaling proteins, led us to wonder what would happen if corals were exposed to a member of the human TNFSF (HuTNFα). HuTNFα was found to bind directly to coral cells, increase caspase activity, cause apoptotic blebbing and cell death, and finally induce coral bleaching. Next, immortalized human T cells (Jurkats) expressing a functional death receptor pathway (WT) and a corresponding Fas-associated death domain protein (FADD) KO cell line were exposed to a coral TNFSF member (AdTNF1) identified and purified here. AdTNF1 treatment resulted in significantly higher cell death (P < 0.0001) in WT Jurkats compared with the corresponding FADD KO, demonstrating that coral AdTNF1 activates the H. sapiens death receptor pathway. Taken together, these data show remarkable conservation of the TNF-induced apoptotic response representing 550 My of functional conservation. evolution immunity | cytokines | Cnidarians | climate change | invertebrate immunity

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Section: Discussionmentioning

confidence: 99%

Evolution of TNF-induced apoptosis reveals 550 My of functional conservation

Quistad

Stotland

Barott

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In cells in which MKRN1 was ablated, anti-Fas-or TRAIL-dependent cell death was efficiently blocked by zVAD-fmk and a caspase-8 inhibitor, but not by necrostatin-1 (nec-1), a necroptosis inhibitor (Supplementary Fig. S4a-c) 20,28,29 . These results allowed us to eliminate the possible involvement of necroptosis.…”

Section: Depletion Of Mkrn1 Induces Dr-mediated Extrinsic Apoptosismentioning

confidence: 99%

“…However, phosphorylation of FADD, the only post-translational modification that FADD is known to undergo, is not involved in the induction of apoptosis. Rather, this modification seems to be essential for the pro-survival roles of nuclear-localized phospho-FADD [20][21][22][23] . Other post-translational modifications affecting the apoptotic and necroptotic activities of FADD have yet to be identified.…”

mentioning

confidence: 99%

Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis

et al. 2012

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Fas-associated protein with death domain (FADD) is a pivotal component of death receptormediated extrinsic apoptosis and necroptosis. Here we show that FADD is regulated by makorin Ring Finger Protein 1 (mKRn1) E3 ligase-mediated ubiquitination and proteasomal degradation. mKRn1 knockdown results in FADD protein stabilization and formation of the rapid deathinducing signalling complex, which causes hypersensitivity to extrinsic apoptosis by facilitating caspase-8 and caspase-3 cleavage in response to death signals. We also show that mKRn1 and FADD are involved in the regulation of necrosome formation and necroptosis upon caspase inhibition. Downregulation of mKRn1 results in severe defects of tumour growth upon tumour necrosis factor-related apoptosis-inducing ligand treatment in a xenograft model using mDAmB-231 breast cancer cells. suppression of tumour growth by mKRn1 depletion is relieved by simultaneous FADD knockdown. our data reveal a novel mechanism by which fas-associated protein with death domain is regulated via an ubiquitination-induced degradation pathway. A poptosis, or programmed cell death, can be initiated by intrinsic or extrinsic pathways 1,2 . Intrinsic pathways are triggered by mitochondrial permeabilization, which results in the release of cytochrome c and the formation of an apoptosome complex, leading to caspase-9 activation 3 . Extrinsic pathways can be induced by activation of death receptors (DRs), such as TNFR1, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors and Fas/CD95 by their corresponding ligands; receptor activation triggers the formation of the death-inducing signalling complex (DISC) or TNFR complex II, which comprises caspase-8 and fas-associated protein with death domain (FADD). These complexes ultimately activate caspase-8, thereby causing extrinsic apoptosis 3,4 . In addition to inducing extrinsic apoptosis, caspase-8 and FADD are known to suppress necroptosis under various conditions [5][6][7][8][9][10][11] .DR downstream pathways are regulated in various ways. For example, cFLIP (cellular FLICE inhibitory protein) competes with caspase-8 for binding to FADD, preventing DISC formation 12 . The levels and activities of cFLIP are controlled by numerous factors including NF-κB, Akt, JNK, Srk and ITCH [13][14][15][16][17] . CARP-1 and -2, which are E3 ubiquitin ligases for caspase-8, are also known to suppress TRAIL activation 18 . Post-translational modifications such as O-glycosylation, S-nitrosylation and S-palmitoylation of DRs have also been identified to regulate death signalling 19 . However, phosphorylation of FADD, the only post-translational modification that FADD is known to undergo, is not involved in the induction of apoptosis. Rather, this modification seems to be essential for the pro-survival roles of nuclear-localized phospho-FADD [20][21][22][23] . Other post-translational modifications affecting the apoptotic and necroptotic activities of FADD have yet to be identified.Here, we show that Makorin Ring Finger Protein 1 (MKRN1), an...

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“…This FADD-dependent complex, referred to as complex II, further augments caspase-8 activation and cell death (26,27). We therefore performed an immunoprecipitation using anti-FADD antibody after treatment with TRAIL or CD95 agonistic antibody and then examined the association of caspase-8 and cFLIP with FADD by Western blotting.…”

Section: Formation Of Dr4/5 or Cd95 Discs Does Not Change Between Mocmentioning

confidence: 99%

GDP-mannose-4,6-dehydratase (GMDS) Deficiency Renders Colon Cancer Cells Resistant to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Receptor- and CD95-mediated Apoptosis by Inhibiting Complex II Formation

Moriwaki

Shinzaki

Miyoshi

2011

Journal of Biological Chemistry

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Background: An impaired TRAIL-induced apoptosis by GMDS deficiency resulted in tumor progression. Results: Caspase-8 activation at FADD-dependent complex II upon TRAIL or CD95L stimulation was inhibited by GMDS deficiency. Conclusion: GMDS regulated the transition from a primary DISC to a secondary complex II upon TRAIL or CD95L stimulation. Significance: Our findings develop a better understanding about death receptor signaling complex.

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FADD: a regulator of life and death

Cited by 163 publications

References 83 publications

Evolution of TNF-induced apoptosis reveals 550 My of functional conservation

Evolution of TNF-induced apoptosis reveals 550 My of functional conservation

Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis

GDP-mannose-4,6-dehydratase (GMDS) Deficiency Renders Colon Cancer Cells Resistant to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Receptor- and CD95-mediated Apoptosis by Inhibiting Complex II Formation

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