Prep1, a novel functional partner of Pbx proteins

Prep1, a novel functional partner of Pbx proteins
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DOI:
10.1093/emboj/17.5.1423
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发表时间:
1998-03-02
期刊:
影响因子:
11.4
通讯作者:
Blasi, F
Blasi, F
中科院分区:
生物学1区
文献类型:
--
作者:
Berthelsen, J;Zappavigna, V;Blasi, F

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人转录因子UEF 3在调节尿激酶纤溶酶原激活物(uPA)基因增强子活性中起重要作用,UEF 3 DNA靶位点是多种生长因子和蛋白酶基因启动子的调控元件。在本文中,我们报道了编码一种新的人类同源结构域蛋白的亚基之一的cDNA的克隆,我们将其命名为Prep 1。Prep 1同源结构域属于同源结构域的TALE类,与TGIF和Meis 1蛋白的那些最密切相关,并且像这些一样,识别TGACAG基序。我们进一步鉴定了另一个UEF 3亚基作为Pbx蛋白家族的成员。与已知与Pbx相互作用的其他蛋白质不同,Prep 1与Pbx形成稳定的复合物,而不依赖于DNA结合。Prep 1和Pbx的异源二聚化导致对uPA启动子的TGACAG靶位点的强DNA结合亲和力。总体而言,这些数据表明Prep 1是体内Pbx的稳定细胞内伴侣。
The human transcription factor, UEF3, is important in regulating the activity of the urokinase plasminogen activator (uPA) gene enhancer, The UEF3 DNA target site is a regulatory element in the promoters of several growth factor and protease genes, We reported previously that purified UEF3 is a complex of several subunits, In this paper we report the cloning of the cDNA of one of the subunits which encodes for a novel human homeodomain protein, which we]have termed Prep1, The Prep1 homeodomain belongs to the TALE class of homeodomains, is most closely related to those of the TGIF and Meis1 proteins, and like these, recognizes a TGACAG motif, We further identify the other UEF3 subunit as a member of the Pbx protein family, Unlike other proteins known to interact with Pbx, Prep1 forms a stable complex with Pbx independent of DNA binding. Heterodimerization of Prep1 and Pbx results in a strong DNA binding affinity towards the TGACAG target site of the uPA promoter, Overall, these data indicate that Prep1 is a stable intracellular partner of Pbx in vivo.