Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators
Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators
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DOI：
10.1093/emboj/17.12.3398
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发表时间：
1998-06-15
期刊：
影响因子：
11.4
通讯作者：
Losson, R
中科院分区：
文献类型：
--
作者：
Huang, NW;vom Baur, E;Losson, R
NSD 1是一种新的2588个氨基酸的小鼠核蛋白，其直接与几种核受体（NR）的配体结合域（LBD）相互作用。NSD 1含有SET结构域和多个PHD指。除了在阳性和阴性果蝇染色体调节子中发现的这些保守结构域之外，NSD 1还含有两个不同的NR相互作用结构域，NID-L和NID+L，它们分别表现出NR辅阻遏物和辅激活物中发现的NID的结合特性。NID-L而不是NID+L与视黄酸受体（RAR）和甲状腺激素受体（TR）的未配体LBD相互作用，并且这种相互作用被阻止辅阻遏物结合和apo-NR的转录沉默的LED α-螺旋1中的突变严重削弱。NID+L而不是NID-L与RAR、TR、类视黄醇X受体（RXR）和雌激素受体（ER）的配体LBD相互作用，这种相互作用被阻止配体诱导的转录激活功能AF-2的共激活因子结合的LED α-螺旋1中的突变所消除。NR盒基序（LxxLL）的新变体（FxxLL）存在于NID+L中，并且是NSD 1与holo-LBD结合所需的。有趣的是，NSD 1含有单独的抑制和激活结构域。因此，NSD 1可能定义了一类新的双功能转录中介因子，在配体存在和不存在的情况下发挥不同的作用。
NSD1, a novel 2588 amino acid mouse nuclear protein that interacts directly with the ligand-binding domain (LBD) of several nuclear receptors (NRs), has been identified and characterized. NSD1 contains a SET domain and multiple PHD fingers. In addition to these conserved domains found in both positive and negative Drosophila chromosomal regulators, NSD1 contains two distinct NR interaction domains, NID-L and NID+L that exhibit binding properties of NIDs found in NR corepressors and coactivators, respectively. NID-L, but not NID+L, interacts with the unliganded LBDs of retinoic acid receptors (RAR) and thyroid hormone receptors (TR), and this interaction is severely impaired by mutations in the LED alpha-helix 1 that prevent binding of corepressors and transcriptional silencing by apo-NRs, NID+L, but not NID-L, interacts with the liganded LBDs of RAR, TR, retinoid X receptor (RXR), and estrogen receptor (ER), and this interaction is abrogated by mutations in the LED alpha-helix 1 that prevent binding of coactivators of the ligand-induced transcriptional activation function AF-2, A novel variant (FxxLL) of the NR box motif (LxxLL) is present in NID+L and is required for the binding of NSD1 to holo-LBDs. Interestingly, NSD1 contains separate repression and activation domains. Thus, NSD1 may define a novel class of bifunctional transcriptional intermediary factors playing distinct roles in both the presence and absence of ligand.