Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation

Hongxiu Li, Masayuki Kobayashi, Marzenna Blonska, Yun You, Xin Lin

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Stimulation of cells with tumor necrosis factor (TNFα) triggers a recruitment of various signaling molecules, such as RIP, to the TNFα receptor 1 complex, leading to activation of NF-κB. Previous studies indicate that RIP plays an essential role for TNFα-induced NF-κB activation, but the molecular mechanism by which RIP mediates TNFα signals to activate NF-κB is not fully defined. Earlier studies suggest that RIP undergoes a ligand-dependent ubiquitination. However, it remains to be determined whether the ubiquitination of RIP is required for TNFα-induced NF-κB activation. In this study, we have identified Lys377 of RIP as the functional ubiquitination site, because mutating this residue to arginine completely abolished RIP-mediated NF-κB activation. The K377R mutation of RIP cannot undergo ligand-dependent ubiquitination and fails to recruit its downstream signaling components into the TNFα receptor 1 complex. Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFα-induced NF-κB activation.

Original languageEnglish (US)
Pages (from-to)13636-13643
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number19
DOIs
StatePublished - May 12 2006
Externally publishedYes

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Ubiquitination
Tumor Necrosis Factor-alpha
Chemical activation
Tumor Necrosis Factor Receptors
Ligands
Arginine
Mutation
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation. / Li, Hongxiu; Kobayashi, Masayuki; Blonska, Marzenna; You, Yun; Lin, Xin.

In: Journal of Biological Chemistry, Vol. 281, No. 19, 12.05.2006, p. 13636-13643.

Research output: Contribution to journalArticle

Li, Hongxiu ; Kobayashi, Masayuki ; Blonska, Marzenna ; You, Yun ; Lin, Xin. / Ubiquitination of RIP is required for tumor necrosis factor α-induced NF-κB activation. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 19. pp. 13636-13643.
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