Receptor-interacting protein shuttles between cell death and survival signaling pathways.
Cross-talk between apoptosis and survival signaling pathways is crucial for regulating tissue processes and mitigating disease. We report that anoikis-apoptosis triggered by loss of extracellular matrix contacts-activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated survival pathways. RIP's death domain was critical for RIP and Fas association to mediate anoikis. Fas or RIP attenuation reduced this association and suppressed anoikis, whereas their overexpression had the reverse effect. Overexpressing FAK restored RIP and FAK association and inhibited anoikis. Thus, RIP shuttles between CD95/Fas death and FAK survival signaling to mediate anoikis.
Kamarajan
Pachiyappan
P
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Bunek
Julius
J
Lin
Yong
Y
Nunez
Gabriel
G
Kapila
Yvonne L
YL
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D053222:Fas Ligand Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases