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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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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DOI: https://doi.org/10.1038/sj.onc.1210863
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