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Molecular and Cellular Biology, March 2000, p. 1699-1712, Vol. 20, No. 5
U4341 and
U248,4 INSERM-Institut Curie, 75005 Paris, CEPH Fondation Jean Dausset, 75010 Paris,2 and Unité des Virus
Oncogènes, UA1644 CNRS, Département des Biotechnologies,
Institut Pasteur, 75015 Paris,3 France
Received 28 May 1999/Returned for modification 3 August
1999/Accepted 15 November 1999
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
posttranslational modifications, alternative splicing, or mutations.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cloning and Characterization of SCHIP-1, a Novel
Protein Interacting Specifically with Spliced Isoforms and
Naturally Occurring Mutant NF2 Proteins
*
Corresponding author. Mailing address: CEPH Fondation
Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France. Phone: 33 1 53 72 51 20. Fax: 33 1 53 72 51 92. E-mail:
goutebroze{at}cephb.fr.
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