Chfr is required for tumor suppression and Aurora A regulation

Xiaochun Yu, Katherine Minter-Bykhouse, Liviu Malureanu, Wei Meng Zhao, Dongwei Zhang, Carolin J. Merkle, Irene M. Ward, Hideyuki Saya, Guowei Fang, Jan Van Deursen, Junjie Chen

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Tumorigenesis is a consequence of loss of tumor suppressors and activation of oncogenes. Expression of the mitotic checkpoint protein Chfr is lost in 20-50% of primary tumors and tumor cell lines. To explore whether downregulation of Chfr contributes directly to tumorigenesis, we generated Chfr knockout mice. Chfr-deficient mice are cancer-prone, develop spontaneous tumors and have increased skin tumor incidence after treatment with dimethylbenz(a)anthracene. Chfr deficiency leads to chromosomal instability in embryonic fibroblasts and regulates the mitotic kinase Aurora A, which is frequently upregulated in a variety of tumors. Chfr physically interacts with Aurora A and ubiquitinates Aurora A both in vitro and in vivo. Collectively, our data suggest that Chfr is a tumor suppressor and ensures chromosomal stability by controlling the expression levels of key mitotic proteins such as Aurora A.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalNature genetics
Volume37
Issue number4
DOIs
Publication statusPublished - 2005 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Chfr is required for tumor suppression and Aurora A regulation'. Together they form a unique fingerprint.

  • Cite this

    Yu, X., Minter-Bykhouse, K., Malureanu, L., Zhao, W. M., Zhang, D., Merkle, C. J., Ward, I. M., Saya, H., Fang, G., Van Deursen, J., & Chen, J. (2005). Chfr is required for tumor suppression and Aurora A regulation. Nature genetics, 37(4), 401-406. https://doi.org/10.1038/ng1538