ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer.
ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer.
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DOI：
10.1158/0008-5472.can-11-0853
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发表时间：
2011-10-15
期刊：
影响因子：
11.2
通讯作者：
Lin SY
中科院分区：
文献类型：
--
作者：
Hu R;Peng G;Dai H;Breuer EK;Stemke-Hale K;Li K;Gonzalez-Angulo AM;Mills GB;Lin SY
乳腺癌的全基因组测序研究最近发现了锌指蛋白668（ZNF 668）的频繁突变，其功能尚未确定。在这里，我们报告，ZNF 668是一个核仁蛋白，物理相互作用，并调节p53和它的负调节MDM2。ZNF 668通过与MDM2结合调节MDM2的自泛素化及其介导p53泛素化和降解的能力。ZNF668缺陷也损害DNA损伤诱导的p53稳定。RNAi介导的ZNF 668敲低足以转化正常乳腺上皮细胞。ZNF 668在体外能有效抑制乳腺癌细胞的增殖，在体内能有效抑制乳腺癌细胞的致瘤性。综上所述，我们的研究确定ZNF 668作为一种新的乳腺肿瘤抑制基因，其功能是调节p53的稳定性。
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. RNAi-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.