RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF‐κB and is processed during apoptosis
Open Access
- 1 December 2002
- journal article
- research article
- Published by Springer Nature in EMBO Reports
- Vol. 3 (12) , 1201-1208
- https://doi.org/10.1093/embo-reports/kvf236
Abstract
RIP1 and its homologs, RIP2 and RIP3, form part of a family of Ser/Thr kinases that regulate signal transduction processes leading to NF‐κB activation. Here, we identify RIP4 (DIK/PKK) as a novel member of the RIP kinase family. RIP4 contains an N‐terminal RIP‐like kinase domain and a C‐terminal region characterized by the presence of 11 ankyrin repeats. Overexpression of RIP4 leads to activation of NF‐κB and JNK. Kinase inactive RIP4 or a truncated version containing the ankyrin repeats have a dominant negative (DN) effect on NF‐κB induction by multiple stimuli. RIP4 binds to several members of the TRAF protein family, and DN versions of TRAF1, TRAF3 and TRAF6 inhibit RIP4‐induced NF‐κB activation. Moreover, RIP4 is cleaved after Asp340 and Asp378 during Fas‐induced apoptosis. These data suggest that RIP4 is involved in NF‐κB and JNK signaling and that caspase‐dependent processing of RIP4 may negatively regulate NF‐κB‐dependent pro‐survival or pro‐inflammatory signals.Keywords
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