Receptor-interacting Protein Shuttles between Cell Death and Survival Signaling Pathways |
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| Authors: | Pachiyappan Kamarajan Julius Bunek Yong Lin Gabriel Nunez Yvonne L Kapila |
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| Institution: | *Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078; ;†Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM; and ;‡Department of Pathology, School of Medicine, University of Michigan, Ann Arbor, MI 48109-0938 |
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| Abstract: | 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. |
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