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癌抑制蛋白 NF2(merlin)のカルパイン依存性分解による新しい腫瘍発生機構 : 木村麗新^1,3, 古閑比佐志¹, 荒木令江¹, 竹島秀雄^２, 西　徹^２, 山嶋哲盛^４, 西道隆臣⁵, 山崎俊樹^３, 森竹浩三^３, 佐谷秀行^１, 中尾光善^１（熊本大・医・^１腫瘍, ^２脳外, ^３島根医大・医・脳外, ^４金沢 大・医・脳外, ^５理研・脳科学・神経蛋白制御）

The involvement of calpain-dependent proteolysis of the tumor suppressor NF2(merlin) in schwannomas and meningiomas : Yoriyoshi KIMURA^1,3, Hisashi KOGA¹, Norie ARAKI¹, Hideo TAKESHIMA², Tohru NISHI², Trtsumori YAMASHIMA⁴, Takaomi C.SAIDO⁵, Toshiki YAMASAKI³, Kouzo MORITAKE³, Hideyuki SAYA¹, Mitsuyoshi NAKAO¹ (¹Dept.Tumor. Genet.Biol., ²Dept.Neurosurg.Kumamoto Univ.Sch.Med., ³Dept.Neurosurg.Shimane Med.Univ., ⁴Dept.Neurosurg.Kanazawa Univ.Sch.Med., ⁵Labo. for Proteolytic Neoroscience,RIKEN Brain Science Inst.)

Neurofibromatosis type 2(NF2) protein, merlin or schwannomin, is a tumor suppressor, and NF2 gene has been found mutated in the majority of schwannomas and meningiomas. Despite NF2-dependency, the presence of tumors lacking detectable NF2 gene mutations suggests different mechanisms for inactivating merlin. The present study demonstrated the cleavage of merlin by ubiquitous calpain, and the marked activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in a portion of schwannomas and meningiomas is the first example of tumorigenesis linked to the calpain-mediated proteolytic pathway.