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Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression

Oncogene volume 24, pages 1946–1957 (2005)Cite this article

Abstract

Meningiomas are common central nervous system tumors; however, the molecular mechanisms underlying their pathogenesis are largely undefined. Previous work has implicated Protein 4.1B as an important tumor suppressor involved in the development of these neoplasms. In this report, we demonstrate that the U2 domain is necessary and sufficient for the ability of Protein 4.1B to function as a meningioma growth suppressor. Using a series of truncation and deletion constructs of DAL-1 (a fragment of Protein 4.1B that retains all the growth suppressive properties), we narrowed the domain required for 4.1B growth suppression to a fragment containing a portion of the FERM domain and the U2 domain using clonogenic assays on meningioma cells. Deletion of the U2 domain in the context of the full-length DAL-1 molecule eliminated growth suppressor function, as measured by thymidine incorporation and caspase-3 activation. Moreover, targeting the U2 domain to the plasma membrane using a membrane localization signal (MLS) reduced cell proliferation, similar to wild-type DAL-1. Collectively, the data suggest that the U2 domain, when properly targeted to the plasma membrane, contains all the residues necessary for mediating Protein 4.1B growth suppression.

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Acknowledgements

We thank Angela Hirbe and Carrie Haipek for their technical assistance during the execution of this project and Ezequiel Surace for his critical review of this manuscript. These studies were supported by grants from the National Institutes of Health (NS41520) and the US Army (DAMD17-04-1-0266) to DHG and from the National Cancer Institute (1-F32-CA-097816-01) to VAR.

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  1. Department of Neurology, Washington University School of Medicine, St Louis, MO, 63110, USA

    Victoria A Robb, Mark A Gerber, Elizabeth K Hart-Mahon & David H Gutmann

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  1. Victoria A Robb
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Correspondence to David H Gutmann.

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Robb, V., Gerber, M., Hart-Mahon, E. et al. Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene 24, 1946–1957 (2005). https://doi.org/10.1038/sj.onc.1208335

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