ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression
ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression
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DOI：
10.1016/j.bbrc.2016.06.124
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发表时间：
2016-09-02
影响因子：
3.1
通讯作者：
Iwamoto, Sadahiko
中科院分区：
文献类型：
--
作者：
Watanabe, Kazuhisa;Nakayama, Kazuhiro;Iwamoto, Sadahiko
一个糖尿病易感基因，免疫球蛋白样结构域受体2 (Ildr2)，编码一种定位于内质网膜的跨膜蛋白，与肝脏脂质代谢密切相关。Ildr2短暂过表达的ob/ob小鼠肝脏脂肪变性得到缓解。然而，ILDR2影响肝脂质代谢变化的分子机制尚不清楚。本研究旨在鉴定ILDR2相互作用蛋白，以进一步阐明ILDR2在脂质稳态中作用的分子机制。我们利用串联亲和纯化标记技术纯化了含有ildr2的蛋白复合物，并鉴定出Kruppel c2h2型锌指蛋白家族成员ZNF70是一种新的ildr2相互作用蛋白。我们证明ZNF70与ZFP64相互作用，并通过结合HES1启动子激活HES1转录。此外，在ildr2敲低的HepG2细胞中，HES1基因表达增加，其中ZNF70从细胞质易位到细胞核，表明ZNF70在与ILDR2-ZNF70复合物分离后迁移到细胞核，激活了HES1的转录。这些结果支持了ILDR2和HES1基因表达之间的新联系，并表明ILDR2参与了肝脂肪变性的新途径。(C) 2016 Elsevier Inc.版权所有。
A diabetes susceptibility gene, immunoglobulin-like domain containing receptor 2 (Ildr2), encodes a transmembrane protein localized to the endoplasmic reticulum membrane that is closely related to hepatic lipid metabolism. The livers of ob/ob mice in which Ildr2 is transiently overexpressed are relieved of hepatic steatosis. However, the molecular mechanisms through which ILDR2 affects these changes in hepatic lipid metabolism remain unknown. This study aimed to identify ILDR2-interacting proteins to further elucidate the molecular mechanisms underlying the role of ILDR2 in lipid homeostasis. We purified ILDR2-containing protein complexes using tandem affinity purification tagging and identified ZNF70, a member of the Kruppel C2H2-type zinc finger protein family, as a novel ILDR2-interacting protein. We demonstrated that ZNF70 interacts with ZFP64 and activates HES1 transcription by binding to the HES1 promoter. In addition, HES1 gene expression is increased in ILDR2-knockdown HepG2 cells, in which ZNF70 is translocated from the cytoplasm to the nucleus, suggesting that ZNF70 migration to the nucleus after dissociating from the ILDR2-ZNF70 complex activates HES1 transcription. These results support a novel link between ILDR2 and HES1 gene expression and suggest that ILDR2 is involved in a novel pathway in hepatic steatosis. (C) 2016 Elsevier Inc. All rights reserved.