Repression of Smad3 activity by histone demethylase SMCX/JARID1C
Repression of Smad3 activity by histone demethylase SMCX/JARID1C
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DOI：
10.1016/j.bbrc.2007.12.013
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发表时间：
2008-02-08
影响因子：
3.1
通讯作者：
Janknecht, Ralf
中科院分区：
文献类型：
--
作者：
Kim, Tae-Dong;Shin, Sook;Janknecht, Ralf
SMCX/JARID 1C最近被证明是一种历史性的H3赖氨酸4（H3 K4）脱甲基酶。在这里，我们已经确定了SMCX亚型，主要存在于细胞质中，但仍然有效地去甲基化三甲基化H3 K4。SMCX的脱甲基酶活性需要几个功能结构域，并且还能够通过氨基酸204-493形成同聚体。此外，SMCX与转化生长因子-β（TGF-β）的介体Smad 3物理相互作用，并且SMCX的过表达抑制Smad 3激活转录的能力。因此，SMCX是一种新的Smad 3辅阻遏物，可以拮抗TGF-β/Smad 3信号通路的肿瘤抑制活性，从而有助于肿瘤发生。事实上，SMCX在前列腺肿瘤和腺瘤中过表达，表明SMCX可能是一种新的癌基因。(c)2007年爱思唯尔公司All rights reserved.
SMCX/JARID1C was recently shown to be a historic H3 lysine 4 (H3K4) demethylase. Here, we have identified an SMCX isoform that predominantly resides in the cytoplasm, but still efficiently demethylates trimethylated H3K4. SMCX requires several functional domains for its demethylase activity and is also capable of forming homomers through amino acids 204-493. Further, SMCX physically interacts with Smad3, a mediator of transforming growth factor-beta (TGF-beta), and overexpression of SMCX inhibits the ability of Smad3 to activate transcription. Thus, SMCX is a novel Smad3 corepressor that may antagonize the tumor suppressing activity of the TGF-beta/ Smad3 signaling pathway and thereby contribute to tumorigenesis. Indeed, SMCX is overexpressed in prostate tumors and seminomas, suggesting that SMCX might be a novel oncogene. (c) 2007 Elsevier Inc. All rights reserved.