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The interaction of p62 with RIP links the atypical PKCs to NF‐κB activation
Author(s) -
Sanz Laura,
Sanchez Pilar,
Lallena MariaJosé,
DiazMeco María T.,
Moscat Jorge
Publication year - 1999
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/18.11.3044
Subject(s) - biology , nfkb1 , kappa , nf κb , microbiology and biotechnology , cancer research , genetics , signal transduction , transcription factor , gene , linguistics , philosophy
The two members of the atypical protein kinase C (aPKC) subfamily of isozymes (ζPKC and λ/ιPKC) are involved in the control of nuclear factor κB (NF‐κB) through IKKβ activation. Here we show that the previously described aPKC‐binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo . p62 bridges the aPKCs to RIP, whereas the aPKCs link IKKβ to p62. In this way, a signaling cascade of interactions is established from the TNF‐R1 involving TRADD/RIP/p62/aPKCs/IKKβ. These observations define a novel pathway for the activation of NF‐κB involving the aPKCs and p62. Consistent with this model, the expression of a dominant‐negative mutant λ/ιPKC impairs RIP‐stimulated NF‐κB activation. In addition, the expression of either an N‐terminal aPKC‐binding domain of p62, or its C‐terminal RIP‐binding region are sufficient to block NF‐κB activation. Furthermore, transfection of an antisense construct of p62 severely abrogates NF‐κB activation. Together, these results demonstrate that the interaction of p62 with RIP serves to link the atypical PKCs to the activation of NF‐κB by the TNFα signaling pathway.