Nac1 interacts with the POZ-domain transcription factor, Miz1.

Nac1 interacts with the POZ-domain transcription factor, Miz1.
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DOI:
10.1042/bsr20140049
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发表时间:
2014-06-05
期刊:
影响因子:
4
通讯作者:
Wright SC
Wright SC
中科院分区:
生物学3区
文献类型:
--
作者:
Stead MA;Wright SC

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Nac1(伏隔核1)是一种POZ(痘病毒和锌指)结构域转录抑制因子,在卵巢浆液性癌中高水平表达。在此我们确定Nac1是POZ结构域转录激活因子Miz1(Myc相互作用锌指蛋白1)的一种新型相互作用伙伴,并且通过化学交联我们表明这种关联是由Nac1和Miz1的POZ结构域的异二聚体相互作用介导的。在哺乳动物细胞核内的离散小体中发现有Nac1,并且我们证实了在转染的HeLa细胞中Miz1重新定位到这些结构。我们表明在卵巢癌细胞中通过小干扰RNA(siRNA)介导的Nac1敲低导致Miz1靶基因产物p21Cip1水平升高。因此,Nac1与Miz1的相互作用可能与其在卵巢癌中的肿瘤发生机制有关。 Nac1是一种转录抑制因子,与卵巢浆液性癌有关。在此我们表明Nac1与转录因子Miz1相互作用,并提出这种相互作用可能有助于肿瘤发生。
Nac1 (nucleus accumbens 1) is a POZ (poxvirus and zinc finger)-domain transcriptional repressor that is expressed at high levels in ovarian serous carcinoma. Here we identify Nac1 as a novel interacting partner of the POZ-domain transcriptional activator, Miz1 (Myc-interacting zinc-finger protein 1), and using chemical crosslinking we show that this association is mediated by a heterodimeric interaction of the Nac1 and Miz1 POZ domains. Nac1 is found in discrete bodies within the nucleus of mammalian cells, and we demonstrate the relocalization of Miz1 to these structures in transfected HeLa cells. We show that siRNA (small interfering RNA)-mediated knockdown of Nac1 in ovarian cancer cells results in increased levels of the Miz1 target gene product, p21Cip1. The interaction of Nac1 with Miz1 may thus be relevant to its mechanism of tumourigenesis in ovarian cancer. Nac1 is a transcriptional repressor that has been implicated in ovarian serous carcinoma. Here we show that Nac1 interacts with the transcription factor Miz1, and suggest that this interaction may contribute to tumourigenesis.