| Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations. | |
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MedLine Citation:
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PMID: 10561699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D H Gutmann; C A Haipek; K Hoang Lu |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of neuroscience research Volume: 58 ISSN: 0360-4012 ISO Abbreviation: J. Neurosci. Res. Publication Date: 1999 Dec |
Date Detail:
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Created Date: 2000-01-05 Completed Date: 2000-01-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 706-16 Citation Subset: IM |
Copyright Information:
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Copyright 1999 Wiley-Liss, Inc. |
Affiliation:
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Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA. gutmannd@neuro.wustl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western DNA, Complementary Exons / genetics Humans Membrane Proteins / genetics* Microtubules / chemistry Neurofibromatosis 2 / genetics* Neurofibromin 2 Protein Structure, Tertiary / physiology |
| Grant Support | |
ID/Acronym/Agency:
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NS35848/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/Membrane Proteins; 0/Neurofibromin 2 |
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