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The atypical PKC‐interacting protein p62 channels NF‐κB activation by the IL‐1–TRAF6 pathway
Author(s) -
Sanz Laura,
DiazMeco María T.,
Nakano Hiroyasu,
Moscat Jorge
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.7.1576
Subject(s) - biology , traf2 , microbiology and biotechnology , signal transduction , tumor necrosis factor alpha , nfkb1 , kinase , transfection , nf κb , protein kinase c , transcription factor , cell culture , immunology , genetics , tumor necrosis factor receptor , gene
The atypical protein kinase C (aPKC)‐interacting protein, p62, has previously been shown to interact with RIP, linking these kinases to NF‐κB activation by tumor necrosis factor α (TNFα). The aPKCs have been implicated in the activation of IKKβ in TNFα‐stimulated cells and have been shown to be activated in response to interleukin‐1 (IL‐1). Here we demonstrate that the inhibition of the aPKCs or the down‐regulation of p62 severely abrogates NF‐κB activation by IL‐1 and TRAF6, suggesting that both proteins are critical intermediaries in this pathway. Consistent with this we show that p62 selectively interacts with the TRAF domain of TRAF6 but not that of TRAF5 or TRAF2 in co‐transfection experiments. The binding of endogenous p62 to TRAF6 is stimulus dependent, reinforcing the notion that this is a physiologically relevant interaction. Furthermore, we demonstrate that the N‐terminal domain of TRAF6, which is required for signaling, interacts with ζPKC in a dimerization‐dependent manner. Together, these results indicate that p62 is an important intermediary not only in TNFα but also in IL‐1 signaling to NF‐κB through the specific adapters RIP and TRAF6.