PMID- 10795740 OWN - NLM STAT- MEDLINE DCOM- 20000523 LR - 20230413 IS - 1074-7613 (Print) IS - 1074-7613 (Linking) VI - 12 IP - 4 DP - 2000 Apr TI - The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. PG - 419-29 AB - The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are essential effectors in TNF signaling. To understand the mechanism by which RIP and TRAF2 regulate TNF-induced activation of the transcription factor NF-kappaB, we investigated their respective roles in TNF-R1-mediated IKK activation using both RIP-/- and TRAF2-/- fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation. Moreover, we demonstrated that IKK is recruited to the TNF-R1 complex through TRAF2 upon TNF treatment and that IKK activation requires the presence of RIP in the same complex. FAU - Devin, A AU - Devin A AD - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Cook, A AU - Cook A FAU - Lin, Y AU - Lin Y FAU - Rodriguez, Y AU - Rodriguez Y FAU - Kelliher, M AU - Kelliher M FAU - Liu, Z AU - Liu Z LA - eng GR - R01 GM061298/GM/NIGMS NIH HHS/United States PT - Journal Article PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Antigens, CD) RN - 0 (Macromolecular Substances) RN - 0 (NF-kappa B) RN - 0 (Proteins) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Recombinant Fusion Proteins) RN - 0 (TNF Receptor-Associated Factor 2) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (RIPK1 protein, human) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) RN - EC 2.7.11.10 (CHUK protein, human) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 2.7.11.10 (IKBKB protein, human) RN - EC 2.7.11.10 (IKBKE protein, human) SB - IM MH - Antigens, CD/analysis/chemistry/*physiology MH - Apoptosis/*physiology MH - Cells, Cultured MH - Enzyme Activation MH - Fibroblasts/cytology MH - Humans MH - I-kappa B Kinase MH - Macromolecular Substances MH - NF-kappa B/*physiology MH - Protein Serine-Threonine Kinases/chemistry/*physiology MH - Proteins/*physiology MH - Receptor-Interacting Protein Serine-Threonine Kinases MH - Receptors, Tumor Necrosis Factor/analysis/chemistry/*physiology MH - Receptors, Tumor Necrosis Factor, Type I MH - Recombinant Fusion Proteins/physiology MH - Signal Transduction/*physiology MH - TNF Receptor-Associated Factor 2 MH - *Transcription, Genetic MH - Transfection EDAT- 2000/05/05 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/05/05 09:00 PHST- 2000/05/05 09:00 [pubmed] PHST- 2000/06/08 09:00 [medline] PHST- 2000/05/05 09:00 [entrez] AID - S1074-7613(00)80194-6 [pii] AID - 10.1016/s1074-7613(00)80194-6 [doi] PST - ppublish SO - Immunity. 2000 Apr;12(4):419-29. doi: 10.1016/s1074-7613(00)80194-6.