ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer

Ruozhen Hu, Guang Peng, Hui Dai, Eun Kyoung Breuer, Katherine Stemke-Hale, Kaiyi Li, Ana M. Gonzalez-Angulo, Gordon Mills, Shiaw Yih Lin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Genome-wide sequencing studies in breast cancer have recently identified frequent mutations in the zinc finger protein 668 (ZNF668), the function of which is undefined. Here, we report that ZNF668 is a nucleolar protein that physically interacts with and regulates p53 and its negative regulator MDM2. Through MDM2 binding, ZNF668 regulated autoubiquitination of MDM2 and its ability to mediate p53 ubiquitination and degradation. ZNF668 deficiency also impaired DNA damage-induced stabilization of p53. RNA interference-mediated knockdown of ZNF668 was sufficient to transform normal mammary epithelial cells. ZNF668 effectively suppressed breast cancer cell proliferation in vitro and tumorigenicity in vivo. Taken together, our studies identify ZNF668 as a novel breast tumor suppressor gene that functions in regulating p53 stability.

Original languageEnglish (US)
Pages (from-to)6524-6534
Number of pages11
JournalCancer Research
Volume71
Issue number20
DOIs
StatePublished - Oct 15 2011
Externally publishedYes

Fingerprint

Zinc Fingers
Breast Neoplasms
Neoplasms
Proteins
Protein Deficiency
Ubiquitination
Nuclear Proteins
RNA Interference
Tumor Suppressor Genes
DNA Damage
Breast
Epithelial Cells
Cell Proliferation
Genome
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hu, R., Peng, G., Dai, H., Breuer, E. K., Stemke-Hale, K., Li, K., ... Lin, S. Y. (2011). ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. Cancer Research, 71(20), 6524-6534. https://doi.org/10.1158/0008-5472.CAN-11-0853

ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. / Hu, Ruozhen; Peng, Guang; Dai, Hui; Breuer, Eun Kyoung; Stemke-Hale, Katherine; Li, Kaiyi; Gonzalez-Angulo, Ana M.; Mills, Gordon; Lin, Shiaw Yih.

In: Cancer Research, Vol. 71, No. 20, 15.10.2011, p. 6524-6534.

Research output: Contribution to journalArticle

Hu, R, Peng, G, Dai, H, Breuer, EK, Stemke-Hale, K, Li, K, Gonzalez-Angulo, AM, Mills, G & Lin, SY 2011, 'ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer', Cancer Research, vol. 71, no. 20, pp. 6524-6534. https://doi.org/10.1158/0008-5472.CAN-11-0853
Hu, Ruozhen ; Peng, Guang ; Dai, Hui ; Breuer, Eun Kyoung ; Stemke-Hale, Katherine ; Li, Kaiyi ; Gonzalez-Angulo, Ana M. ; Mills, Gordon ; Lin, Shiaw Yih. / ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. In: Cancer Research. 2011 ; Vol. 71, No. 20. pp. 6524-6534.
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