Molecular insights into NF2/Merlin tumor suppressor function Journal Article
| Authors: | Cooper, J.; Giancotti, F. G. |
| Article Title: | Molecular insights into NF2/Merlin tumor suppressor function |
| Abstract: | The FERM domain protein Merlin, encoded by the NF2 tumor suppressor gene, regulates cell proliferation in response to adhesive signaling. The growth inhibitory function of Merlin is induced by intercellular adhesion and inactivated by joint integrin/receptor tyrosine kinase signaling. Merlin contributes to the formation of cell junctions in polarized tissues, activates anti-mitogenic signaling at tight-junctions, and inhibits oncogenic gene expression. Thus, inactivation of Merlin causes uncontrolled mitogenic signaling and tumorigenesis. Merlin's predominant tumor suppressive functions are attributable to its control of oncogenic gene expression through regulation of Hippo signaling. Notably, Merlin translocates to the nucleus where it directly inhibits the CRL4DCAF1 E3 ubiquitin ligase, thereby suppressing inhibition of the Lats kinases. A dichotomy in NF2 function has emerged whereby Merlin acts at the cell cortex to organize cell junctions and propagate anti-mitogenic signaling, whereas it inhibits oncogenic gene expression through the inhibition of CRL4DCAF1 and activation of Hippo signaling. The biochemical events underlying Merlin's normal function and tumor suppressive activity will be discussed in this Review, with emphasis on recent discoveries that have greatly influenced our understanding of Merlin biology. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
| Keywords: | signal transduction; protein phosphorylation; unclassified drug; review; nonhuman; protein function; protein localization; protein analysis; enzyme inhibition; protein degradation; protein protein interaction; transcription factor; tumor suppressor gene; protein processing; ubiquitination; enzyme inactivation; membrane protein; cell membrane; protein dephosphorylation; protein structure; hermes antigen; structure analysis; ubiquitin protein ligase e3; sumoylation; cytoskeleton; nuclear localization signal; merlin; nf2 gene; ezrin; moesin; radixin; contact inhibition; alpha catenin; hippo signaling pathway; cytoplasm protein; priority journal; neurofibromatosis type 2; crl4 e3 ubiquitin ligase; ddb1 and cul4-associated factor 1; angiomotin; crl4 ddb1 and cul4 associated factor 1; ddb1 and cul4 associated factor 1; nherf protein; tap protein; yap protein; convergent evolution; hippo signaling |
| Journal Title: | FEBS Letters |
| Volume: | 588 |
| Issue: | 16 |
| ISSN: | 0014-5793 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2014-08-19 |
| Start Page: | 2743 |
| End Page: | 2752 |
| Language: | English |
| DOI: | 10.1016/j.febslet.2014.04.001 |
| PROVIDER: | scopus |
| PMCID: | PMC4111995 |
| PUBMED: | 24726726 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2014 -- CODEN: FEBLA -- Source: Scopus |
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