The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas.
Neurofibromatosis type 2 (NF2) protein, also known as merlin or schwannomin, is a tumor suppressor, and NF2 is mutated in most schwannomas and meningiomas. Although these tumors are dependent on NF2, some lack detectable NF2 mutations, which indicates that alternative mechanisms exist for inactivating merlin. Here, we demonstrate cleavage of merlin by the ubiquitous protease calpain and considerable activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway.
Kimura
Y
Y
Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Honjo, Japan.
Koga
H
H
Araki
N
N
Mugita
N
N
Fujita
N
N
Takeshima
H
H
Nishi
T
T
Yamashima
T
T
Saido
T C
TC
Yamasaki
T
T
Moritake
K
K
Saya
H
H
Nakao
M
M
D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D004789:Enzyme Activation; D016515:Genes, Neurofibromatosis 2; D005910:Glioma / Q000378:metabolism*; D005982:Glutathione Transferase / Q000096:biosynthesis; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009442:Neurilemmoma / Q000378:metabolism*; D025581:Neurofibromin 2; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D008565:Membrane Proteins; D025581:Neurofibromin 2; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D002154:Calpain