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Functional interaction between tumor suppressor menin and activator of S-phase kinase

Robert W Schnepp1, Zhaoyuan Hou, Haoren Wang

  • 1Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.

Cancer Research
|September 18, 2004
PubMed

Insights

Menin, a tumor suppressor, is essential for regulating cell proliferation. Menin interacts with activator of S-phase kinase (ASK) to inhibit cell growth, demonstrating a novel link in cell cycle control.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Multiple endocrine neoplasia type I (MEN1) is a hereditary syndrome involving tumors in multiple endocrine organs.
  • The Men1 gene encodes the tumor suppressor protein menin, which is implicated in tumor development.
  • The precise role of menin in regulating cell proliferation and its mechanism of action remain unclear.

Purpose of the Study:

  • To investigate the role of menin in cell proliferation control.
  • To elucidate the molecular mechanism by which menin regulates cell proliferation.
  • To identify potential interactions between menin and key cell cycle regulators.

Main Methods:

  • Gene targeting to create menin-null cells and complementation studies.
  • Analysis of cell proliferation rates in response to menin manipulation.
  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • In vitro kinase assays and cell-based proliferation assays.

Main Results:

  • Targeted disruption of the Men1 gene resulted in enhanced cell proliferation.
  • Complementation of menin-null cells with menin reduced cell proliferation.
  • Menin was found to interact with activator of S-phase kinase (ASK), a critical component of the Cdc7/ASK complex.
  • Wild-type menin, but not disease-related mutants lacking ASK interaction, effectively repressed ASK-induced cell proliferation.

Conclusions:

  • Menin plays an essential role in the repression of cell proliferation.
  • Menin's interaction with ASK is crucial for its tumor-suppressive function.
  • These findings establish a functional link between menin and ASK in regulating cell proliferation and provide insights into MEN1 pathogenesis.

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