Document Detail

Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations.
MedLine Citation:
PMID:  10561699     Owner:  NLM     Status:  MEDLINE    
The neurofibromatosis 2 (NF2) tumor suppressor gene product, merlin (schwannomin) forms an intramolecular association that is required for negative growth regulation in vitro and in vivo. In an effort to develop a molecular model for merlin relevant to its tumor suppressor function, we further characterized merlin intramolecular folding. We now demonstrate that merlin forms two intramolecular associations, one between the amino terminal (N-term) domain and the carboxyl terminal (C-term) domain and another within the amino terminal domain (N-term/N-term) itself. The N-term/C-term domain interaction requires contact between residues 302-308 in the N-term and an intact exon 17 (residues 580-595) in the C-term domain. In addition, we demonstrate that the N-term/N-term domain self-interaction is required for N-term/C-term domain association. Lastly, we identify NF2 patient mutations that dramatically reduce each of these interactions in vitro. Based on these findings, we propose a model for merlin folding critical to its ability to function as a tumor suppressor protein.
D H Gutmann; C A Haipek; K Hoang Lu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  58     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-05     Completed Date:  2000-01-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  706-16     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Wiley-Liss, Inc.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
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MeSH Terms
Blotting, Western
DNA, Complementary
Exons / genetics
Membrane Proteins / genetics*
Microtubules / chemistry
Neurofibromatosis 2 / genetics*
Neurofibromin 2
Protein Structure, Tertiary / physiology
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Membrane Proteins; 0/Neurofibromin 2

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