Journal article
RalB GTPase-Mediated Activation of the IκB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival
Cell (Cambridge), Vol.127(1), pp.157-170
2006
DOI: 10.1016/j.cell.2006.08.034
PMID: 17018283
Abstract
The monomeric RalGTPases, RalA and RalB are recognized as components of a regulatory framework supporting tumorigenic transformation. Specifically, RalB is required to suppress apoptotic checkpoint activation, the mechanistic basis of which is unknown. Reported effector proteins of RalB include the Sec5 component of the exocyst, an octameric protein complex implicated in tethering of vesicles to membranes. Surprisingly, we find that the RalB/Sec5 effector complex directly recruits and activates the atypical IκB kinase family member TBK1. In cancer cells, constitutive engagement of this pathway, via chronic RalB activation, restricts initiation of apoptotic programs typically engaged in the context of oncogenic stress. Although dispensable for survival in a nontumorigenic context, this pathway helps mount an innate immune response to virus exposure. These observations define the mechanistic contribution of RalGTPases to cancer cell survival and reveal the RalB/Sec5 effector complex as a component of TBK1-dependent innate immune signaling.
Details
- Title: Subtitle
- RalB GTPase-Mediated Activation of the IκB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival
- Creators
- Yuchen Chien - Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USASungchan Kim - Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USARon Bumeister - Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USAYueh-Ming Loo - Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USASung Won Kwon - Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USACynthia L Johnson - Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USAMirey G Balakireva - Institut Curie, Inserm U-548, Paris, FranceYves Romeo - Institut Curie, Inserm U-548, Paris, FranceLevy Kopelovich - National Institutes of Health/National Cancer Institute/Division of Cancer Prevention, Bethesda, MD 20892, USAMichael Gale - Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USACharles Yeaman - Department of Anatomy and Cell Biology, University of Iowa, 51 Newton Rd., Iowa City, IA 52242, USAJacques H Camonis - Institut Curie, Inserm U-548, Paris, FranceYingming Zhao - Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USAMichael A White - Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.127(1), pp.157-170
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2006.08.034
- PMID
- 17018283
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2006
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025474002771
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