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Chfr is required for tumor suppression and Aurora A regulation

Xiaochun Yu1, Katherine Minter-Dykhouse, Liviu Malureanu

  • 1Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.

Nature Genetics
|March 29, 2005
PubMed

Insights

Loss of the Chfr protein, a tumor suppressor, leads to cancer and chromosomal instability. Chfr normally controls mitotic kinase Aurora A, preventing tumor development.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genetics

Background:

  • Tumorigenesis involves tumor suppressor loss and oncogene activation.
  • The mitotic checkpoint protein Chfr is downregulated in 20-50% of tumors.
  • The role of Chfr in tumorigenesis requires further investigation.

Purpose of the Study:

  • To determine if Chfr downregulation contributes to cancer.
  • To investigate the mechanism by which Chfr functions as a tumor suppressor.

Main Methods:

  • Generation and analysis of Chfr knockout mice.
  • Assessment of tumor development and chromosomal stability in Chfr-deficient mice.
  • Investigation of the interaction between Chfr and Aurora A kinase.

Main Results:

  • Chfr-deficient mice are cancer-prone, developing spontaneous tumors.
  • Chfr deficiency causes chromosomal instability in embryonic fibroblasts.
  • Chfr interacts with and ubiquitinates Aurora A, a kinase often upregulated in tumors.

Conclusions:

  • Chfr acts as a tumor suppressor by maintaining chromosomal stability.
  • Chfr controls the expression of key mitotic proteins like Aurora A.
  • Loss of Chfr function is a contributing factor to tumorigenesis.

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