NLRs at the intersection of cell death and immunity.
Inflammation is a crucial element of the host response to cellular insult. Pathogen-induced inflammation includes a molecular pathway which proceeds through activation of the protease caspase-1 to the release of the inflammatory cytokines interleukin-1 (IL-1) and IL-18. Importantly, pathogens may also induce forms of cell death that have inherently pro-inflammatory features. Here, we review recent evidence demonstrating that NLR (nucleotide-binding domain, leucine-rich repeat containing) family proteins serve as a common component of both caspase-1-activated apoptotic pathways and caspase-independent necrotic pathways. Parallels are drawn between NLR protein function and the activity of structurally similar proteins involved in cell death: the apoptotic mediator APAF1 (apoptotic-protease-activating factor 1) and the plant disease resistance NBS-LRR (nucleotide-binding site leucine-rich repeats) proteins.
Ting
Jenny P-Y
JP
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA. jenny_ting@med.unc.edu
Willingham
Stephen B
SB
Bergstralh
Daniel T
DT
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000502:physiology; D020170:Caspase 1 / Q000378:metabolism; D003141:Communicable Diseases / Q000276:immunology / Q000473:pathology; D024243:HMGB1 Protein / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D000090263:Leucine-Rich Repeat Proteins; D000070576:NLR Proteins; D009336:Necrosis; D011506:Proteins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D024243:HMGB1 Protein; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D000090263:Leucine-Rich Repeat Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1