A functional association between merlin and HEI10, a cell cycle regulator

Oncogene. 2006 Jul 27;25(32):4389-98. doi: 10.1038/sj.onc.1209475. Epub 2006 Mar 13.

Abstract

Merlin and ezrin are homologous proteins with opposite effects on neoplastic growth. Merlin is a tumor suppressor inactivated in the neurofibromatosis 2 disease, whereas upregulated ezrin expression is associated with increased malignancy. Merlin's tumor suppressor mechanism is not known, although participation in cell cycle regulation has been suggested. To characterize merlin's biological activities, we screened for molecules that would interact with merlin but not ezrin. We identified the cyclin B-binding protein and cell cycle regulator HEI10 as a novel merlin-binding partner. The interaction is mediated by the alpha-helical domain in merlin and the coiled-coil domain in HEI10 and requires conformational opening of merlin. The two proteins show partial subcellular colocalization, which depends on cell cycle stage and cell adhesion. Comparison of Schwann cells and schwannoma cultures demonstrated that the distribution of HEI10 depends on merlin expression. In transfected cells, a constitutively open merlin construct affected HEI10 protein integrity. These results link merlin to the cell cycle control machinery and may help to understand its tumor suppressor function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Neurofibromin 2 / biosynthesis
  • Neurofibromin 2 / genetics
  • Neurofibromin 2 / metabolism
  • Neurofibromin 2 / physiology*
  • Rats

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Neurofibromin 2
  • CCNB1IP1 protein, human