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α-Catulin, a Rho signalling component, can regulate NF-κB through binding to IKK-β, and confers resistance to apoptosis

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Abstract

Rho GTPases regulate diverse cellular functions including adhesion, cytokinesis and motility, as well as the activity of the transcription factors NF-κB, serum response factor and C/EBP. α-Catulin, an α-catenin-related protein that shares structural similarities with cytoskeletal linker proteins, facilitates Rho signalling by serving as a scaffold for the Rho-specific guanine nucleotide exchange factor Lbc. We report here that α-catulin also interacts with a key component of the NF-κB signalling pathway, namely the IκB kinase (IKK)-β. In co-immunoprecipitations, α-catulin can bind IKK-β and Lbc. Ectopic expression of α-catulin augmented NF-κB activity, promoted cell migration and increased resistance to apoptosis, whereas knockdown experiments showed the opposite effects. Together, these features suggest that α-catulin has tumorigenic potential.

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Abbreviations

HUVEC:

human umbilical vein endothelial cells

IκB:

inhibitory subunit of NF-κB

IKK-β:

IκBα kinase-β

NF-κB:

nuclear factor-κB

wt:

wild-type

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Acknowledgements

We thank B Gilbert for technical assistance in generating hybridomas, M Karin for providing several of the NF-κB related expression constructs, W Graier for RhoA and D Toksoz for SRE-Luc. JvH is a postdoctoral researcher with the Fund for Scientific Research (FWO), Flanders. This work was supported by grants from the Austrian Science foundation (SFB 005-11, P16765-B13), and by the FWO and the Interuniversity Attraction Poles Programme of the Belgian Science Policy. We thank Dr A Bredan for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria

    C Wiesner, G Winsauer, U Resch, M Hoeth, J A Schmid, B R Binder & R de Martin

  2. Department for Molecular Biomedical Research, Ghent, Belgium

    J van Hengel & F van Roy

  3. Department of Molecular Biology, Ghent University, Ghent, Belgium

    J van Hengel & F van Roy

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  1. C Wiesner
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  2. G Winsauer
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  3. U Resch
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  4. M Hoeth
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  5. J A Schmid
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  6. J van Hengel
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  7. F van Roy
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  8. B R Binder
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  9. R de Martin
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Correspondence to R de Martin.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Wiesner, C., Winsauer, G., Resch, U. et al. α-Catulin, a Rho signalling component, can regulate NF-κB through binding to IKK-β, and confers resistance to apoptosis. Oncogene 27, 2159–2169 (2008). https://doi.org/10.1038/sj.onc.1210863

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