Characterization of RalB-Sec5-TBK1 function in human oncogenesis.

Methods in Enzymology
Yuchen Chien, Michael A White

Abstract

The Ras-like GTPases, RalA and RalB, are key components of the oncogenic Ras signaling network. Recent evidence suggests that RalA and RalB collaborate to support tumorigenic transformation through distinct cell regulatory events. While RalA is apparently required to bypass normal restraints on cell proliferation, RalB is required to bypass normal restraints on cell survival. A direct Ral effector protein, Sec5, is a subunit of the exocyst complex, and is required to mediate RalB-dependent survival signals in transformed cells. Further analysis identified TBK1, a key mediator of the host defense response to viral challenge, as a novel Sec5 interacting protein essential for the capacity of RalB and Sec5 to deflect cell death in transformed cells. RalB activation promotes a direct interaction between Sec5 and TBK1 that results in TBK1 kinase activation via an unknown mechanism. Accordingly, both RalB and Sec5 are required for initiating host defense pathway activation upon virus infection. These observations revealed a novel relationship between molecular components of cell-autonomous innate immune signaling pathways and oncogenic transformation, and identified TBK1 as a potential target for therapeutic intervention in cancer. He...Continue Reading

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Dec 12, 2001·Nature Cell Biology·Serge MoskalenkoMichael A White
Jul 12, 2003·EMBO Reports·Yuchen Chien, Michael A White
Jul 31, 2003·Trends in Cell Biology·Larry A Feig
Oct 4, 2003·The Journal of Biological Chemistry·Serge MoskalenkoMichael A White
Dec 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sarah M McWhirterTom Maniatis

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Citations

May 3, 2011·Nature Reviews. Drug Discovery·Denise A Chan, Amato J Giaccia
Feb 18, 2010·Therapy·Sapna Trivedi, Eric L Greidinger
May 6, 2016·Frontiers in Cell and Developmental Biology·Magdalena Martin-UrdirozIsabelle Jourdain
Feb 2, 2010·Cell Research·Archana Bommi-Reddy, William G Kaelin
Sep 27, 2016·Journal of Cellular Physiology·Toshiaki TanakaMitsuyoshi Iino
Aug 5, 2015·Journal of Cell Science·Bin Wu, Wei Guo

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