Merlin's tumor suppression linked to inhibition of the E3 ubiquitin ligase CRL4DCAF1

Wei Li, Filippo G. Giancotti

Research output: Contribution to journalReview article

15 Scopus citations

Abstract

The mechanism by which the FERM domain protein Merlin, encoded by the tumor suppressor NF2, restrains cell proliferation is poorly understood. Prior studies have suggested that Merlin exerts its antimitogenic effect by interacting with multiple signaling proteins located at or near the plasma membrane. We have recently observed that Merlin translocates into the nucleus and binds to and inhibits the E3 ubiquitin ligase CRL4DCAF1. Genetic evidence indicates that inactivation of Merlin induces oncogenic gene expression, hyperproliferation, and tumorigenicity by unleashing the activity of CRL4DCAF1. In addition to providing a potential explanation for the diverse effects that loss of Merlin exerts in multiple cell types, these findings suggest that compounds inhibiting CRL4DCAF1 may display therapeutic efficacy in Neurofibromatosis type 2 and other cancers driven by Merlin inactivation.

Original languageEnglish (US)
Pages (from-to)4433-4436
Number of pages4
JournalCell Cycle
Volume9
Issue number22
DOIs
StatePublished - Nov 15 2010

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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