Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors
Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors
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DOI：
10.1093/nar/30.9.2043
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发表时间：
2002-05-01
影响因子：
14.9
通讯作者：
Blasi, F
中科院分区：
文献类型：
--
作者：
Fognani, C;Kilstrup-Nielsen, C;Blasi, F
TALE（三氨基酸环延伸）同源结构域蛋白包括PBC和MEINOX亚家族。MEINOX蛋白与PBC蛋白形成异源二聚体复合物。异二聚化对DNA结合和核定位至关重要。PBC-MEINOX异源二聚体也与HOX蛋白结合DNA，从而调节其DNA结合特异性。因此，TALE蛋白在体内多种发育和分化途径中起着至关重要的作用。我们报告鉴定和表征一个新的人类基因同源的PREP1，称为PREP2。序列比较表明，PREP1和PREP2定义了MEINOX蛋白的一个新的亚家族，不同于MEIS亚家族。PREP2在多种成人组织中表达，并表现出比PREP1更有限的表达模式。PREP2能够与PBC蛋白异二聚化。与PBX1的异二聚化似乎是PREP2和PBX1的核定位所必需的。对PREP1和PREP2的功能特性进行比较发现，PREP2- pbx比PREP1- pbx表现出更快的dna解离速率，表明其在控制基因表达中的作用不同。与PREP1一样，PREP2-PBX异源二聚体能够与HOXB1形成三元配合物。对PREP2的一些体外特性分析表明PREP之间以及PREP与MEIS MEINOX蛋白之间的功能多样化。
TALE (three amino acid loop extension) homeodomain proteins include the PBC and the MEINOX sub-families. MEINOX proteins form heterodimer complexes with PBC proteins. Heterodimerization is crucial to DNA binding and for nuclear localization. PBC-MEINOX heterodimers bind DNA also in combination with HOX proteins, thereby modulating their DNA-binding specificity. TALE proteins therefore play crucial roles in multiple developmental and differentiation pathways in vivo. We report the identification and characterization of a novel human gene homologous to PREP1, called PREP2. Sequence comparisons indicate that PREP1 and PREP2 define a novel sub-family of MEINOX proteins, distinct from the MEIS sub-family. PREP2 is expressed in a variety of human adult tissues and displays a more restricted expression pattern than PREP1. PREP2 is capable of heterodimerizing with PBC proteins. Heterodimerization with PBX1 appears to be essential for nuclear localization of both PREP2 and PBX1. A comparison between the functional properties of PREP1 and PREP2 reveals that PREP2-PBX display a faster DNA-dissociation rate than PREP1-PBX heterodimers, suggesting different roles in controlling gene expression. Like PREP1, PREP2-PBX heterodimers are capable of forming ternary complexes with HOXB1. The analysis of some PREP2 in vitro properties suggests a functional diversification among PREP and between PREP and MEIS MEINOX proteins.