Cloning and characterization of SCHIP-1, a novel protein interacting specifically with spliced isoforms and naturally occurring mutant NF2 proteins

被引:66
作者
Goutebroze, L
Brault, E
Muchardt, C
Camonis, J
Thomas, G
机构
[1] Fdn Jean Dausset, CEPH, F-75010 Paris, France
[2] Inst Curie, INSERM, U434, F-75005 Paris, France
[3] Inst Curie, INSERM, U248, F-75005 Paris, France
[4] Inst Pasteur, Dept Biotechnol, Unite Virus Oncogenes, CNRS,UA1644, F-75015 Paris, France
关键词
D O I
10.1128/MCB.20.5.1699-1712.2000
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The neurofibromatosis type 2 (NF2) protein, known as schwannomin or merlin, is a tumor suppressor involved in NF2-associated and sporadic schwannomas and meningiomas. It is closely related to the ezrin-radixin-moesin family members, implicated in linking membrane proteins to the cytoskeleton. The molecular mechanism allowing schwannomin to function as a tumor suppressor is unknown. In attempt to shed light on schwannomin function, we have identified a novel coiled-coil protein, SCHIP-1, that specifically associates with schwannomin in vitro and in vivo. Within its coiled-coil region, this protein is homologous to human FEZ proteins and the related Caenorhabditis elegans gene product UNC-76. Immunofluorescent staining of transiently transfected cells shows a partial colocalization of SCHIP-1 and schwannomin, beneath the cytoplasmic membrane. Surprisingly, immunoprecipitation assays reveal that in a cellular context, association with SCHIP-1 can be observed only with some naturally occurring mutants of schwannomin, or a schwannomin spliced isoform lacking exons 2 and 3, but not with the schwannomin isoform exhibiting growth-suppressive activity. Our observations suggest that SCHIP-1 interaction with schwannomin is regulated by conformational changes in schwannomin, possibly induced by posttranstational modifications, alternative splicing, or mutations.
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页码:1699 / 1712
页数:14
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