TY - JOUR
T1 - ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer
AU - Hu, Ruozhen
AU - Peng, Guang
AU - Dai, Hui
AU - Breuer, Eun Kyoung
AU - Stemke-Hale, Katherine
AU - Li, Kaiyi
AU - Gonzalez-Angulo, Ana M.
AU - Mills, Gordon B.
AU - Lin, Shiaw Yih
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-11-0853
DO - 10.1158/0008-5472.CAN-11-0853
M3 - Article
C2 - 21852383
AN - SCOPUS:80054030424
SN - 0008-5472
VL - 71
SP - 6524
EP - 6534
JO - Cancer Research
JF - Cancer Research
IS - 20
ER -