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Unformatted text preview: 10.1101/gad.1335605 Access the most recent version at doi: 2005 19: 2265-2277 Genes Dev. Andrea I. McClatchey and Marco Giovannini suppressor, Merlin the NF2 tumor-- Membrane organization and tumorigenesis References http://genesdev.cshlp.org/content/19/19/2265.full.html#related-urls Article cited in: http://genesdev.cshlp.org/content/19/19/2265.full.html#ref-list-1 This article cites 112 articles, 52 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article - sign up in the box at the Topic collections (76 articles) Signal Transduction Articles on similar topics can be found in the following collections http://genesdev.cshlp.org/subscriptions go to: Genes & Development To subscribe to Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press on March 5, 2009 - Published by genesdev.cshlp.org Downloaded from REVIEW Membrane organization and tumorigenesisthe NF2 tumor suppressor, Merlin Andrea I. McClatchey 1,3 and Marco Giovannini 2 1 Massachusetts General Hospital, Center for Cancer Research and Harvard Medical School, Department of Pathology, Charlestown, Massachusetts 02129, USA; 2 Inserm U674, Fondation Jean Dausset-CEPH et Institut Universitaire dHmatologie, Paris, France The NF2 tumor-suppressor gene was cloned more than a decade ago, but the function of its encoded protein, Mer- lin, remains elusive. Merlin, like the closely related ERM proteins, appears to provide regulated linkage be- tween membrane-associated proteins and the actin cyto- skeleton and is therefore poised to function in receiving and interpreting signals from the extracellular milieu. Recent studies suggest that Merlin may coordinate the processes of growth-factor receptor signaling and cell ad- hesion. Varying use of this organizing activity by differ- ent types of cells could provide an explanation for the unique spectrum of tumors associated with NF2 defi- ciency in mammals. The identification of the genetic defect responsible for the familial cancer syndrome Neurofibromatosis type 2 (NF2) nearly 15 years ago yielded the unexpected pros- pect that the encoded tumor suppressor was a cytoskel- eton-associated protein (Rouleau et al. 1993; Trofatter et al. 1993). This was in marked contrast to the known and now classic tumor suppressors p53, Rb, and NF1 that function either to directly control the cell cycle machin- ery in the nucleus, or in the case of NF1, to directly negatively regulate mitogenic Ras signaling (Sherr 2004). Several factors have rendered progress in defining the molecular basis of NF2-associated tumorigenesis slow, including the rare incidence of NF2 in humans, the pau- city of NF2-/- cell lines and technical challenges in studying the NF2-encoded protein, Merlin, which is a novel type of tumor suppressor. However, recent ad- vances, highlighted by the study of NF2 function in sev- eral different model organisms have begun to yield a...
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