Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression
Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression
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DOI：
10.1016/j.yexcr.2006.10.009
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发表时间：
2007-01-15
影响因子：
3.7
通讯作者：
Wang, Yizheng
中科院分区：
文献类型：
--
作者：
Huang, Chuanxin;Jia, Yichang;Wang, Yizheng
Krupple-associated box-containing zinc-finger proteins（KRAB-ZFPs）是转录因子中最大的家族之一。KRAB-ZFP的几个成员调节细胞生长、存活并涉及恶性疾病。然而，大多数成员的特征并不明确，其功能也基本上不为人所知。在这里，我们报告ZNF 23，KRAB-ZFP的成员，抑制细胞周期的进展。ZNF 23蛋白定位于细胞核，在所有检测的正常组织中普遍表达。然而，ZNF 23蛋白的表达水平在人类癌症中丢失或大大降低。ZNF 23的异位表达可导致p27（kip-1）表达增强，细胞生长受到抑制，细胞周期阻滞于G（1）期。通过针对p27（kip-1）的siRNA下调p27（kip-1）可逆转ZNF 23诱导的生长抑制。此外，ZNF 23的生长抑制作用不依赖于p53。缺失分析表明ZNF 23的作用不依赖于其KRAB结构域，而是依赖于C端锌指结构。因此，我们已经确定了一个新的KRAB-ZNF超家族成员的生长抑制能力，其下调可能有助于致癌。(c)2006年爱思唯尔公司All rights reserved.
The Krupple-associated box-containing zinc-finger proteins (KRAB-ZFPs) make up one of the largest family of transcription factors. Several members of the KRAB-ZFPs modulate cell growth, survival and are implicated in malignant disorders. However, most members are not well characterized and their functions are largely unknown. Here we report that ZNF23, a member of KRAB-ZFPs, inhibits cell cycle progression. ZNF23 protein localized to the nucleus and was ubiquitously expressed in all tested normal tissues. However, the expression levels of ZNF23 protein were lost or greatly reduced in human cancer. Ectopic expression of ZNF23 led to enhancement of p27(kip-1) expression, growth inhibition and cell cycle arrest in G(1) phase. Downregulation of p27(kip-1) by siRNA against p27(kip-1) reversed growth inhibition induced by ZNF23. Furthermore, the growth-inhibitory effect of ZNF23 was p53-independent. Deletion analysis revealed that the effect of ZNF23 did not rely on its KRAB domain, but on the C-terminal zinc fingers. Thus, we have identified a new member of KRAB-ZNF superfamily with growth-inhibitory ability and its downregulation may contribute to carcinogenesis. (c) 2006 Elsevier Inc. All rights reserved.