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The merlin tumor suppressor interacts with Ral guanine nucleotide dissociation stimulator and inhibits its activity.
- Source :
-
Oncogene [Oncogene] 2005 Aug 11; Vol. 24 (34), pp. 5355-64. - Publication Year :
- 2005
-
Abstract
- Neurofibromatosis type 2 (NF2) is the most commonly mutated gene in benign tumors of the human nervous system such as schwannomas and meningiomas. The NF2 gene encodes a protein called schwannomin or merlin, which is involved in regulating cell growth and proliferation through protein-protein interactions with various cellular proteins. In order to better understand the mechanism by which merlin exerts its function, yeast two-hybrid screening was performed and Ral guanine nucleotide dissociation stimulator (RalGDS), a downstream molecule of Ras, was identified as a merlin-binding protein. The direct interaction between merlin and RalGDS was confirmed both in vitro and in the NIH3T3 cells. The domain analyses revealed that the broad C-terminal region of merlin (aa 141-595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RalGDS. Functional studies showed that merlin inhibits the RalGDS-induced RalA activation, the colony formation and the cell migration in mammalian cells. These results suggest that merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals.
- Subjects :
- Animals
COS Cells
Cell Movement
Cell Transformation, Neoplastic
Chlorocebus aethiops
Colony-Forming Units Assay
Humans
Immunohistochemistry
Mice
NIH 3T3 Cells
Neurofibromin 2 metabolism
Protein Binding
Two-Hybrid System Techniques
Yeasts
Neurofibromin 2 physiology
ral Guanine Nucleotide Exchange Factor antagonists & inhibitors
ral Guanine Nucleotide Exchange Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 24
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 16007223
- Full Text :
- https://doi.org/10.1038/sj.onc.1208633