TRADD

The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-κB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway.

Image:TNF signaling.jpg-R1. Dashed grey lines represent multiple steps]]

TRADD has been shown to interact with:

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• FADD,{{cite journal | vauthors = Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP | title = Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures | journal = J. Neurochem. | volume = 86 | issue = 5 | pages = 1260–70 | date = September 2003 | pmid = 12911633 | doi = 10.1046/j.1471-4159.2003.01934.x| s2cid = 21971958 | doi-access = free }}{{cite journal | vauthors = Thomas LR, Stillman DJ, Thorburn A | title = Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen | journal = J. Biol. Chem. | volume = 277 | issue = 37 | pages = 34343–8 | date = September 2002 | pmid = 12107169 | doi = 10.1074/jbc.M204169200 | doi-access = free }}
• Keratin 18{{cite journal | vauthors = Inada H, Izawa I, Nishizawa M, Fujita E, Kiyono T, Takahashi T, Momoi T, Inagaki M | title = Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD | journal = J. Cell Biol. | volume = 155 | issue = 3 | pages = 415–26 | date = October 2001 | pmid = 11684708 | pmc = 2150850 | doi = 10.1083/jcb.200103078 }}
• RIPK1,
• STAT1,{{cite journal | vauthors = Wang Y, Wu TR, Cai S, Welte T, Chin YE | title = Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation | journal = Mol. Cell. Biol. | volume = 20 | issue = 13 | pages = 4505–12 | date = July 2000 | pmid = 10848577 | pmc = 85828 | doi = 10.1128/mcb.20.13.4505-4512.2000}}
• TNFRSF1A,{{cite journal | vauthors = Hsu H, Shu HB, Pan MG, Goeddel DV | title = TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways | journal = Cell | volume = 84 | issue = 2 | pages = 299–308 | date = January 1996 | pmid = 8565075 | doi = 10.1016/s0092-8674(00)80984-8| s2cid = 13171355 | doi-access = free }}{{cite journal | vauthors = Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV | title = TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex | journal = Immunity | volume = 4 | issue = 4 | pages = 387–96 | date = April 1996 | pmid = 8612133 | doi = 10.1016/s1074-7613(00)80252-6| doi-access = free }}{{cite journal | vauthors = Jiang Y, Woronicz JD, Liu W, Goeddel DV | title = Prevention of constitutive TNF receptor 1 signaling by silencer of death domains | journal = Science | volume = 283 | issue = 5401 | pages = 543–6 | date = January 1999 | pmid = 9915703 | doi = 10.1126/science.283.5401.543}}{{cite journal | vauthors = Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke M | title = Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling | journal = J. Biol. Chem. | volume = 274 | issue = 15 | pages = 10203–12 | date = April 1999 | pmid = 10187805 | doi = 10.1074/jbc.274.15.10203| doi-access = free }}{{cite journal | vauthors = Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM | title = The receptor for the cytotoxic ligand TRAIL | journal = Science | volume = 276 | issue = 5309 | pages = 111–3 | date = April 1997 | pmid = 9082980 | doi = 10.1126/science.276.5309.111| s2cid = 19984057 }}{{cite journal | vauthors = Shu HB, Takeuchi M, Goeddel DV | title = The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 24 | pages = 13973–8 | date = November 1996 | pmid = 8943045 | pmc = 19479 | doi = 10.1073/pnas.93.24.13973| bibcode = 1996PNAS...9313973S | doi-access = free }}{{cite journal | vauthors = Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D | title = Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1) | journal = Biochem. J. | volume = 417 | issue = 1 | pages = 149–60 | date = January 2009 | pmid = 18939944 | doi = 10.1042/BJ20081885 }}
• TNFRSF25,{{cite journal | vauthors = Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham CJ, Brown R, Farrow SN | title = A death-domain-containing receptor that mediates apoptosis | journal = Nature | volume = 384 | issue = 6607 | pages = 372–5 | date = November 1996 | pmid = 8934525 | doi = 10.1038/384372a0 | s2cid = 4283742 }} and
• TRAF2.{{cite journal | vauthors = Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nat. Cell Biol. | volume = 6 | issue = 2 | pages = 97–105 | date = February 2004 | pmid = 14743216 | doi = 10.1038/ncb1086 | s2cid = 11683986 }}{{cite journal | vauthors = Takeuchi M, Rothe M, Goeddel DV | title = Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 19935–42 | date = August 1996 | pmid = 8702708 | doi = 10.1074/jbc.271.33.19935| doi-access = free }}{{cite journal | vauthors = Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H | title = A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction | journal = Cell | volume = 101 | issue = 7 | pages = 777–87 | date = June 2000 | pmid = 10892748 | doi = 10.1016/s0092-8674(00)80889-2| s2cid = 5928713 | doi-access = free }}{{cite journal | vauthors = Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL | title = Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway | journal = Mol. Cell | volume = 5 | issue = 6 | pages = 1051–7 | date = June 2000 | pmid = 10911999 | doi = 10.1016/s1097-2765(00)80270-1| doi-access = free }}{{cite journal | vauthors = Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H | title = Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death | journal = J. Biol. Chem. | volume = 276 | issue = 39 | pages = 36530–4 | date = September 2001 | pmid = 11479302 | doi = 10.1074/jbc.M104837200 | doi-access = free }}{{cite journal | vauthors = Malinin NL, Boldin MP, Kovalenko AV, Wallach D | title = MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1 | journal = Nature | volume = 385 | issue = 6616 | pages = 540–4 | date = February 1997 | pmid = 9020361 | doi = 10.1038/385540a0 | s2cid = 4366355 }}

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• TRAF
• RIP

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• {{cite journal | vauthors = Baker SJ, Reddy EP | title = Modulation of life and death by the TNF receptor superfamily | journal = Oncogene | volume = 17 | issue = 25 | pages = 3261–70 | year = 1999 | pmid = 9916988 | doi = 10.1038/sj.onc.1202568 | doi-access = free }}
• {{cite journal | vauthors = Hsu H, Shu HB, Pan MG, Goeddel DV | title = TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways | journal = Cell | volume = 84 | issue = 2 | pages = 299–308 | year = 1996 | pmid = 8565075 | doi = 10.1016/S0092-8674(00)80984-8 | s2cid = 13171355 | doi-access = free }}
• {{cite journal | vauthors = Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV | title = TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex | journal = Immunity | volume = 4 | issue = 4 | pages = 387–96 | year = 1996 | pmid = 8612133 | doi = 10.1016/S1074-7613(00)80252-6 | doi-access = free }}
• {{cite journal | vauthors = Boldin MP, Goncharov TM, Goltsev YV, Wallach D | title = Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death | journal = Cell | volume = 85 | issue = 6 | pages = 803–15 | year = 1996 | pmid = 8681376 | doi = 10.1016/S0092-8674(00)81265-9 | s2cid = 7415784 | doi-access = free }}
• {{cite journal | vauthors = Takeuchi M, Rothe M, Goeddel DV | title = Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 19935–42 | year = 1996 | pmid = 8702708 | doi = 10.1074/jbc.271.33.19935 | doi-access = free }}
• {{cite journal | vauthors = Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham CJ, Brown R, Farrow SN | title = A death-domain-containing receptor that mediates apoptosis | journal = Nature | volume = 384 | issue = 6607 | pages = 372–5 | year = 1996 | pmid = 8934525 | doi = 10.1038/384372a0 | s2cid = 4283742 }}
• {{cite journal | vauthors = Shu HB, Takeuchi M, Goeddel DV | title = The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 24 | pages = 13973–8 | year = 1997 | pmid = 8943045 | pmc = 19479 | doi = 10.1073/pnas.93.24.13973 | bibcode = 1996PNAS...9313973S | doi-access = free }}
• {{cite journal | vauthors = Izumi KM, Kieff ED | title = The Epstein–Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF-κB | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 23 | pages = 12592–7 | year = 1997 | pmid = 9356494 | pmc = 25049 | doi = 10.1073/pnas.94.23.12592 | doi-access = free }}
• {{cite journal | vauthors = Wajant H, Johannes FJ, Haas E, Siemienski K, Schwenzer R, Schubert G, Weiss T, Grell M, Scheurich P | title = Dominant-negative FADD inhibits TNFR60-, Fas/Apo1- and TRAIL-R/Apo2-mediated cell death but not gene induction | journal = Curr. Biol. | volume = 8 | issue = 2 | pages = 113–6 | year = 1998 | pmid = 9427646 | doi = 10.1016/S0960-9822(98)70042-9 | s2cid = 6269984 | doi-access = free }}
• {{cite journal | vauthors = Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L | title = Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway | journal = Immunity | volume = 7 | issue = 6 | pages = 821–30 | year = 1998 | pmid = 9430227 | doi = 10.1016/S1074-7613(00)80400-8 | doi-access = free }}
• {{cite journal | vauthors = Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, Vincenz C, Aggarwal BB, Ni J, Dixit VM | title = Identification and functional characterization of DR6, a novel death domain-containing TNF receptor | journal = FEBS Lett. | volume = 431 | issue = 3 | pages = 351–6 | year = 1998 | pmid = 9714541 | doi = 10.1016/S0014-5793(98)00791-1 | hdl = 2027.42/116991 | s2cid = 11151198 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/116991/1/feb2s0014579398007911.pdf | hdl-access = free }}
• {{cite journal | vauthors = Jones SJ, Ledgerwood EC, Prins JB, Galbraith J, Johnson DR, Pober JS, Bradley JR | title = TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1 | journal = J. Immunol. | volume = 162 | issue = 2 | pages = 1042–8 | year = 1999 | doi = 10.4049/jimmunol.162.2.1042 | pmid = 9916731 | doi-access = free }}
• {{cite journal | vauthors = Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke M | title = Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling | journal = J. Biol. Chem. | volume = 274 | issue = 15 | pages = 10203–12 | year = 1999 | pmid = 10187805 | doi = 10.1074/jbc.274.15.10203 | doi-access = free }}
• {{cite journal | vauthors = Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J | title = The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation | journal = EMBO J. | volume = 18 | issue = 11 | pages = 3044–53 | year = 1999 | pmid = 10356400 | pmc = 1171386 | doi = 10.1093/emboj/18.11.3044 }}
• {{cite journal | vauthors = Costanzo A, Guiet C, Vito P | title = c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB | journal = J. Biol. Chem. | volume = 274 | issue = 29 | pages = 20127–32 | year = 1999 | pmid = 10400625 | doi = 10.1074/jbc.274.29.20127 | doi-access = free }}
• {{cite journal | vauthors = Wang Y, Wu TR, Cai S, Welte T, Chin YE | title = Stat1 as a Component of Tumor Necrosis Factor Alpha Receptor 1-TRADD Signaling Complex To Inhibit NF-κB Activation | journal = Mol. Cell. Biol. | volume = 20 | issue = 13 | pages = 4505–12 | year = 2000 | pmid = 10848577 | pmc = 85828 | doi = 10.1128/MCB.20.13.4505-4512.2000 }}
• {{cite journal | vauthors = Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H | title = A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction | journal = Cell | volume = 101 | issue = 7 | pages = 777–87 | year = 2000 | pmid = 10892748 | doi = 10.1016/S0092-8674(00)80889-2 | s2cid = 5928713 | doi-access = free }}
• {{cite journal | vauthors = Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL | title = Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway | journal = Mol. Cell | volume = 5 | issue = 6 | pages = 1051–7 | year = 2000 | pmid = 10911999 | doi = 10.1016/S1097-2765(00)80270-1 | doi-access = free }}

{{Refend}}

• {{MeshName|TRADD+Protein}}

{{PDB Gallery|geneid=8717}}

{{Apoptosis signaling pathway}}