KRAB-containing zinc finger protein ZNF496 inhibits breast cancer cell proliferation by selectively repressing ER alpha activity
KRAB-containing zinc finger protein ZNF496 inhibits breast cancer cell proliferation by selectively repressing ER alpha activity
复制标题
含有 KRAB 的锌指蛋白 ZNF496 通过选择性抑制 ER α 活性来抑制乳腺癌细胞增殖
DOI：
10.1016/j.bbagrm.2018.07.003
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发表时间：
2018
影响因子：
4.7
通讯作者：
Tian Chunyan
中科院分区：
文献类型：
--
作者：
Wang Jinlong;Zhang Xiuyuan;Ling Jiming;Wang Yun;Xu Xiaolin;Liu Yuchen;Jin Chaozhi;Ju Jiyu;Yuan Yanzhi;He Fuchu;Zhao Chunling;Wang Jian;Tian Chunyan
KRAB-containing zinc finger proteins (KZNF) constitute the largest family of transcriptional regulators in humans and play critical roles in normal development and tumorigenesis. However, the function and mechanism of most KZNFs remain unclear. Here, we report that ZNF496, a KZNF family member, interacts with the DNA binding domain (DBD) of estrogen receptor alpha (ERα) via its C2H2 domain. This interaction decreases ERα binding to chromatin DNA and results in the repression of ERα transactivation, the selective suppression of ERα target genes, and ultimately in a reduction of ERα-positive cell growth in the presence of E2. An analysis of clinical data revealed that the downregulation of ZNF496 expression is observed only in ERα-positive and not in ERα-negative breast cancer tissues when compared with that in matched adjacent tissues. Lastly, we also observed that the downregulation of ZNF496 is associated with poor recurrence-free survival among patients with breast cancer. Collectively, our findings demonstrate that ZNF496 is a novel ERα-binding protein that acts as a target gene-specific ERα corepressor and inhibits the growth of ERα-positive breast cancer cells.
