Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).
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 approximately 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.
Division of Neurology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA. scolesd@cshs.org
Daniel R
DR
Scoles
William H
WH
Yong
Yun
Y
Qin
Kolja
K
Wawrowsky
Stefan Matthias
SM
Pulst
D000328:Adult; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008579:Meningioma / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D017253:Neurofibromatoses / Q000378:metabolism; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D039621:Eukaryotic Initiation Factor-3; D025581:Neurofibromin 2; D011994:Recombinant Proteins