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

158 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
Externally publishedYes

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Neoplasms
Chromosomal Instability
Carcinogenesis
Aurora Kinase A
M Phase Cell Cycle Checkpoints
Tumor Cell Line
Oncogenes
Knockout Mice
Proteins
Down-Regulation
Fibroblasts
Skin
Incidence

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Yu, X., Minter-Bykhouse, K., Malureanu, L., Zhao, W. M., Zhang, D., Merkle, C. 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

Chfr is required for tumor suppression and Aurora A regulation. / Yu, Xiaochun; Minter-Bykhouse, Katherine; Malureanu, Liviu; Zhao, Wei Meng; Zhang, Dongwei; Merkle, Carolin J.; Ward, Irene M.; Saya, Hideyuki; Fang, Guowei; Van Deursen, Jan; Chen, Junjie.

In: Nature Genetics, Vol. 37, No. 4, 04.2005, p. 401-406.

Research output: Contribution to journalArticle

Yu, X, Minter-Bykhouse, K, Malureanu, L, Zhao, WM, Zhang, D, Merkle, CJ, Ward, IM, Saya, H, Fang, G, Van Deursen, J & Chen, J 2005, 'Chfr is required for tumor suppression and Aurora A regulation', Nature Genetics, vol. 37, no. 4, pp. 401-406. https://doi.org/10.1038/ng1538
Yu X, Minter-Bykhouse K, Malureanu L, Zhao WM, Zhang D, Merkle CJ et al. Chfr is required for tumor suppression and Aurora A regulation. Nature Genetics. 2005 Apr;37(4):401-406. https://doi.org/10.1038/ng1538
Yu, Xiaochun ; Minter-Bykhouse, Katherine ; Malureanu, Liviu ; Zhao, Wei Meng ; Zhang, Dongwei ; Merkle, Carolin J. ; Ward, Irene M. ; Saya, Hideyuki ; Fang, Guowei ; Van Deursen, Jan ; Chen, Junjie. / Chfr is required for tumor suppression and Aurora A regulation. In: Nature Genetics. 2005 ; Vol. 37, No. 4. pp. 401-406.
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