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 B. Mills, Shiaw Yih Lin

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    16 Scopus citations

    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

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Hu, R., Peng, G., Dai, H., Breuer, E. K., Stemke-Hale, K., Li, K., Gonzalez-Angulo, A. M., Mills, G. B., & 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