Human Molecular Genetics Advance Access published online on February 23, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl021
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1 Division of Neurology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, Room D1089, 8700 Beverly Boulevard, Los Angeles, CA 90048; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90048
* To whom correspondence should be addressed. The neurofibromatosis 2 (NF2) tumor suppressor protein, schwannomin or merlin, is commonly lost upon NF2 gene mutation in benign human brain tumors. We identified the p110 subunit of the eukaryotic initiation factor 3 (eIF3c) as a schwannomin interacting protein. The eIF3 complex consists of
Received November 18, 2005
Revised February 7, 2006
Accepted February 7, 2006
Article
Schwannomin Inhibits Tumorigenesis through Direct Interaction with the Eukaryotic Initiation Factor eIF3c
Daniel R. Scoles 1 *,
William H. Yong 2,
Yun Qin 3,
Kolja Wawrowsky 4,
and
Stefan-M. Pulst 5
2 Department of Pathology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90048
3 Division of Neurology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, Room D1089, 8700 Beverly Boulevard, Los Angeles, CA 90048
4 Confocal Core, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048
5 Division of Neurology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, Room D1089, 8700 Beverly Boulevard, Los Angeles, CA 90048; Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90048; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90048
Daniel R. Scoles, E-mail: ScolesD{at}cshs.org
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Abstract
10 subunits whose functions are only recently becoming known. Interaction between schwannomin and eIF3c suggests a role for schwannomin in eIF3c-mediated regulation of proliferation related to changes in protein translation. We found that schwannomin was most effective for inhibiting cellular proliferation when eIF3c was highly expressed. When we examined these proteins in 14 meningiomas we observed high eIF3c abundance in those that had lost schwannomin expression but low eIF3c abundance in those retaining schwannomin. Consequently, eIF3c appears to be involved in NF2 pathogenesis and deserves to be investigated as a prognostic marker for NF2 and target for treatment of NF2 patient tumors.![]()
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