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

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

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish
Pages (from-to)1946-1957
Number of pages12
JournalOncogene
Volume24
Issue number11
DOIs
StatePublished - Mar 10 2005

Keywords

  • Brain tumor
  • DAL-1
  • Meningioma
  • Protein 4.1B
  • Tumor suppressor

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