TRIP6 is a RIP2-associated common signaling component of multiple NF-kappaB activation pathways.
Receptor-interacting protein 2 (RIP2) is a member of the RIP kinase family that has been shown to be crucially involved in inflammation, innate and adaptive immune responses. The physiological and pathological roles of RIP2 are mediated through its involvement in multiple NF-kappaB activation pathways, including those triggered by tumor necrosis factor (TNF), interleukin 1 (IL-1), Toll-like receptor 2 (TLR2), TLR3, TLR4 and Nod1. In this report, we identified the LIM-domain-containing protein TRIP6 as a RIP2-interacting protein in yeast two-hybrid screens. In mammalian cells, TRIP6 interacts with RIP2 in a TNF- or IL-1-dependent manner. Overexpression of TRIP6 potentiates RIP2-mediated NF-kappaB activation in a dose-dependent manner. The LIM domains of TRIP6 are responsible for its interaction with RIP2. TRIP6 also interacts with TRAF2, a protein that is crucially involved in TNF signaling, as well as the IL-1 receptor, TLR2 and Nod1. Overexpression of TRIP6 potentiates NF-kappaB activation by TNF, IL-1, TLR2 or Nod1, whereas a dominant negative mutant or RNA-interference construct of TRIP6 inhibits NF-kappaB activation by TNF, IL-1, TLR2 or Nod1. Moreover, TRIP6 also potentiates RIP2- and Nod1-mediated ERK activation. These data have established a physical and functional association between TRIP6 and RIP2, and suggest that RIP2's involvement in multiple NF-kappaB and ERK activation pathways is mediated through TRIP6.
Li
Lianyun
L
Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China.
Bin
Liang-Hua
LH
Li
Fu
F
Liu
Yi
Y
Chen
Danying
D
Zhai
Zhonghe
Z
Shu
Hong-Bing
HB
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D060588:LIM Domain Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020798:Two-Hybrid System Techniques; D050807:ets-Domain Protein Elk-1
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D060588:LIM Domain Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C092282:PSMC5 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D050807:ets-Domain Protein Elk-1; D017346:Protein Serine-Threonine Kinases; C506249:RIPK1 protein, human; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities