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Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

Wei Li1, Jonathan Cooper, Matthias A Karajannis

  • 1Cell Biology Program, Sloan–Kettering Institute for Cancer Research, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, Box 216, New York, New York 10065, USA.

EMBO Reports
|April 7, 2012
PubMed

Insights

The NF2 tumor suppressor Merlin inhibits cell growth by contacting cells and regulating gene expression in the nucleus. It also maintains cell adhesion and polarity at the cell cortex.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Contact inhibition is crucial for tissue organization and preventing cancer.
  • Merlin, a FERM domain protein encoded by the NF2 tumor suppressor gene, mediates contact inhibition.
  • Merlin was traditionally thought to function at the plasma membrane, inhibiting growth signals and activating the Hippo pathway.

Purpose of the Study:

  • To elucidate the multifaceted roles of Merlin in cellular signaling and gene expression.
  • To investigate Merlin's nuclear functions beyond its known cortical roles.
  • To understand Merlin's contribution to epithelial adhesion and polarity.

Main Methods:

  • Investigated Merlin's interactions with CRL4DCAF1 E3 ubiquitin ligase.
  • Analyzed Merlin's effects on gene expression programs.
  • Examined Merlin's role in recruiting Par3 and aPKC to cell junctions.
  • Assessed Merlin's impact on tight junction assembly.

Main Results:

  • Merlin inhibits the CRL4DCAF1 E3 ubiquitin ligase in the nucleus, inducing growth suppression.
  • Merlin promotes epithelial adhesion and polarity by organizing E-cadherin and tight junctions.
  • Merlin functions at both the cell cortex and nucleus.

Conclusions:

  • Merlin exhibits dual localization and function, acting at the cell cortex and nucleus.
  • Merlin's nuclear activity involves direct inhibition of CRL4DCAF1, leading to growth suppression.
  • Merlin's cortical activity is essential for establishing epithelial adhesion and polarity, akin to beta-catenin's functions.

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