The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription

The histone methyltransferase, NSD2, enhances androgen receptor-mediated transcription
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DOI:
10.1016/j.febslet.2009.05.038
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发表时间:
2009-06-18
期刊:
影响因子:
3.5
通讯作者:
Yoon, Ho-Geun
Yoon, Ho-Geun
中科院分区:
生物学3区
文献类型:
--
作者:
Kang, Hee-Bum;Choi, Youngsok;Yoon, Ho-Geun

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在本研究中,我们发现NSD 2通过其HMG结构域与雄激素受体(AR)的DNA结合结构域特异性地相互作用,并且在配体的存在下,NSD 2和AR的核转位都被增强。此外,我们还证明了NSD 2的过表达,而不是NSD 2(DSET)HMT活性缺陷型突变体,以剂量依赖性方式增强PSA的mRNA水平。染色质免疫沉淀试验表明,NSD 2蛋白被招募到PSA基因的增强子区域的AR激动剂增强的方式。总之,这些结果揭示了NSD 2在AR介导的转录中的潜在作用,暗示NSD 2在前列腺癌发生中的作用。(uniprotkb:O 96028)物理相互作用(MI:0914)伴α AR(uniprotkb:P10275)通过抗标签共免疫沉淀(MI:0007)MINT-7103748:NSD 2(uniprotkb:O 96028)物理相互作用(MI:0915)伴α AR(uniprotkb:P10275)通过两个杂交(MI:0018)MINT-7103800,MINT-7103819:α AR(uniprotkb:P10275)结合(MI:0407)至NSD 2(uniprotkb:O 96028)通过下拉(MI:0096)MINT-7103785:NSD 2(uniprotkb:O 96028)共定位(MI:0403)伴α AR(uniprotkb:P10275)(MI:0416)MINT-7103733:P53(uniprotkb:P04637)通过双杂交(MI:0018)与α AR(uniprotkb:P10275)物理相互作用(MI:0915)(C)2009欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
In this study, we discovered that NSD2 specifically interacts with the DNA-binding domain of androgen receptor (AR) via its HMG domain, and the nuclear translocation of both NSD2 and AR is enhanced in the presence of ligand. Furthermore, we also demonstrated that the over expression of NSD2, but not of NSD2 (DSET) HMT-activity defective mutant, enhanced the mRNA level of PSA in a dose-dependent manner. A chromatin immunoprecipitation assay showed that NSD2 protein is recruited to the enhancer region of the PSA gene by AR in an agonist-enhanced manner. Taken together, these results uncover a potential role for NSD2 in AR-mediated transcription, implicating NSD2 in prostate carcinogenesis.Structured summary:MINT-7103766: NSD2 (uniprotkb: O96028) physically interacts (MI: 0914) with alpha AR (uniprotkb: P10275) by anti tag coimmunoprecipitation (MI: 0007)MINT-7103748: NSD2 (uniprotkb: O96028) physically interacts (MI: 0915) with alpha AR (uniprotkb: P10275) by two hybrid (MI: 0018)MINT-7103800, MINT-7103819: alpha AR (uniprotkb: P10275) binds (MI: 0407) to NSD2 (uniprotkb: O96028) by pull down (MI: 0096)MINT-7103785: NSD2 (uniprotkb: O96028) colocalizes (MI: 0403) with alpha AR (uniprotkb: P10275) by fluorescence microscopy (MI: 0416)MINT-7103733: P53 (uniprotkb: P04637) physically interacts (MI: 0915) with alpha AR (uniprotkb: P10275) by two hybrid (MI: 0018) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.