RIP1, a kinase on the crossroads of a cell's decision to live or die.
Binding of inflammatory cytokines to their receptors, stimulation of pathogen recognition receptors by pathogen-associated molecular patterns, and DNA damage induce specific signalling events. A cell that is exposed to these signals can respond by activation of NF-kappaB, mitogen-activated protein kinases and interferon regulatory factors, resulting in the upregulation of antiapoptotic proteins and of several cytokines. The consequent survival may or may not be accompanied by an inflammatory response. Alternatively, a cell can also activate death-signalling pathways, resulting in apoptosis or alternative cell death such as necrosis or autophagic cell death. Interplay between survival and death-promoting complexes continues as they compete with each other until one eventually dominates and determines the cell's fate. RIP1 is a crucial adaptor kinase on the crossroad of these stress-induced signalling pathways and a cell's decision to live or die. Following different upstream signals, particular RIP1-containing complexes are formed; these initiate only a limited number of cellular responses. In this review, we describe how RIP1 acts as a key integrator of signalling pathways initiated by stimulation of death receptors, bacterial or viral infection, genotoxic stress and T-cell homeostasis.
Festjens
N
N
Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical Research, VIB and Ghent University, Ghent, Belgium.
Vanden Berghe
T
T
Cornelis
S
S
Vandenabeele
P
P
D000818:Animals; D016923:Cell Death; D004249:DNA Damage; D006706:Homeostasis; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism
D053218:Receptors, Death Domain; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases