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 schwan nomin, is a tumor suppressor, and NF2 is mutated in most schwannomas a nd 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 tu mors. Increased proteolysis of merlin by calpain in some schwannomas a nd meningiomas exemplifies tumorigenesis linked to the calpain-mediate d proteolytic pathway.