The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation.

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Citation

Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J

The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation.

EMBO J. 1999 Jun 1;18(11):3044-53.

PubMed ID
10356400 [ View in PubMed
]
Abstract

The two members of the atypical protein kinase C (aPKC) subfamily of isozymes (zetaPKC and lambda/iotaPKC) are involved in the control of nuclear factor kappaB (NF-kappaB) through IKKbeta 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 IKKbeta to p62. In this way, a signaling cascade of interactions is established from the TNF-R1 involving TRADD/RIP/p62/aPKCs/IKKbeta. These observations define a novel pathway for the activation of NF-kappaB involving the aPKCs and p62. Consistent with this model, the expression of a dominant-negative mutant lambda/iotaPKC impairs RIP-stimulated NF-kappaB 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-kappaB activation. Furthermore, transfection of an antisense construct of p62 severely abrogates NF-kappaB activation. Together, these results demonstrate that the interaction of p62 with RIP serves to link the atypical PKCs to the activation of NF-kappaB by the TNFalpha signaling pathway.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tumor necrosis factor receptor superfamily member 1AP19438Details
Inhibitor of nuclear factor kappa-B kinase subunit betaO14920Details
Protein kinase C iota typeP41743Details
Protein kinase C zeta typeQ05513Details
Receptor-interacting serine/threonine-protein kinase 1Q13546Details