Reactome | TRAF2 ubiquitinates cIAP1,2 in cIAP1,2:TRAF1:TRAF2:TRAF3:NIK

TRAF2 ubiquitinates cIAP1,2 in cIAP1,2:TRAF1:TRAF2:TRAF3:NIK

Stable Identifier

R-HSA-5668414

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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TRAF2 ubiquitinates cIAP1,2 in cIAP1,2:TRAF1:TRAF2:TRAF3:NIK

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Following recruitment to receptor, TRAF2 mediates K63-linked polyubiquitination of cIAP1 and cIAP2. In addition to being an adaptor that recruits cIAP1/2 and TRAF3 to the receptor TRAF2 is also an E3 that activates cIAP1/2, through their K63-linked ubiquitination. This K63-linked ubiquitination stimulates the K48-ubiquitin ligase function of cIAP1/2 and may impose a change in the substrate specificity of cIAP1/2. Thus, rather than ubiquitinating NIK, cIAP1/2 ubiquitinates TRAF3 leading to its degradation (Vallabhapurapu et al. 2008, Wallach & Kovalenko 2008).

Literature References

PubMed ID	Title	Journal	Year
18997794	Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK Mahoney, DJ, Wang, Y, Shiba, T, Mak, TW, Yeh, WC, Cheng, G, Dempsey, PW, He, J, Cheung, HH, Korneluk, RG, Yang, X, Zarnegar, BJ	Nat. Immunol.	2008
18997792	Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling Zhang, W, Tseng, PH, Matsuzawa, A, Vignali, DA, Bergsagel, PL, Keats, JJ, Karin, M, Wang, H, Vallabhapurapu, S	Nat. Immunol.	2008