Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About MCB
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Molecular and Cellular Biology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About MCB
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Articles

NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth

Marianne F. James, Sangyeul Han, Carolyn Polizzano, Scott R. Plotkin, Brendan D. Manning, Anat O. Stemmer-Rachamimov, James F. Gusella, Vijaya Ramesh
Marianne F. James
1Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sangyeul Han
1Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carolyn Polizzano
1Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott R. Plotkin
2Department of Neurology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brendan D. Manning
3Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anat O. Stemmer-Rachamimov
4Molecular Neuro-Oncology Laboratory, Division of Neuropathology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James F. Gusella
1Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vijaya Ramesh
1Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, Massachusetts 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ramesh@helix.mgh.harvard.edu
DOI: 10.1128/MCB.01581-08
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Inactivating mutations of the neurofibromatosis 2 (NF2) gene, NF2, result predominantly in benign neurological tumors, schwannomas and meningiomas, in humans; however, mutations in murine Nf2 lead to a broad spectrum of cancerous tumors. The tumor-suppressive function of the NF2 protein, merlin, a membrane-cytoskeleton linker, remains unclear. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a novel mediator of merlin's tumor suppressor activity. Merlin-deficient human meningioma cells and merlin knockdown arachnoidal cells, the nonneoplastic cell counterparts of meningiomas, exhibit rapamycin-sensitive constitutive mTORC1 activation and increased growth. NF2 patient tumors and Nf2-deficient mouse embryonic fibroblasts demonstrate elevated mTORC1 signaling. Conversely, the exogenous expression of wild-type merlin isoforms, but not a patient-derived L64P mutant, suppresses mTORC1 signaling. Merlin does not regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase-mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion. In conclusion, the deregulation of mTORC1 activation underlies the aberrant growth and proliferation of NF2-associated tumors and may restrain the growth of these lesions through negative feedback mechanisms, suggesting that rapamycin in combination with phosphoinositide 3-kinase inhibitors may be therapeutic for NF2.

  • Copyright © 2009 American Society for Microbiology
View Full Text
PreviousNext
Back to top
Download PDF
Citation Tools
NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth
Marianne F. James, Sangyeul Han, Carolyn Polizzano, Scott R. Plotkin, Brendan D. Manning, Anat O. Stemmer-Rachamimov, James F. Gusella, Vijaya Ramesh
Molecular and Cellular Biology Jul 2009, 29 (15) 4250-4261; DOI: 10.1128/MCB.01581-08

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Molecular and Cellular Biology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth
(Your Name) has forwarded a page to you from Molecular and Cellular Biology
(Your Name) thought you would be interested in this article in Molecular and Cellular Biology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
NF2/Merlin Is a Novel Negative Regulator of mTOR Complex 1, and Activation of mTORC1 Is Associated with Meningioma and Schwannoma Growth
Marianne F. James, Sangyeul Han, Carolyn Polizzano, Scott R. Plotkin, Brendan D. Manning, Anat O. Stemmer-Rachamimov, James F. Gusella, Vijaya Ramesh
Molecular and Cellular Biology Jul 2009, 29 (15) 4250-4261; DOI: 10.1128/MCB.01581-08
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

cell proliferation
Neurofibromin 2
transcription factors

Related Articles

Cited By...

About

  • About MCB
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #MCBJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0270-7306; Online ISSN: 1098-5549