The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas

Yoriyoshi Kimurau, Hisashi Koga, Norie Araki, Norifumi Mugita, Naoyuki Fujita, Hideo Takeshima, Tohru Nishi, Tetsumori Yamashima, Takaomi C. Saido, Toshiki Yamasaki, Kouzo Moritake, Hideyuki Saya, Mitsuyoshi Nakao

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)915-922
Number of pages8
JournalNature medicine
Volume4
Issue number8
DOIs
Publication statusPublished - 1998 Aug

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kimurau, Y., Koga, H., Araki, N., Mugita, N., Fujita, N., Takeshima, H., Nishi, T., Yamashima, T., Saido, T. C., Yamasaki, T., Moritake, K., Saya, H., & Nakao, M. (1998). The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas. Nature medicine, 4(8), 915-922. https://doi.org/10.1038/nm0898-915