Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor region are both required for optimal transformation of Rat1 fibroblasts
Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor region are both required for optimal transformation of Rat1 fibroblasts
复制标题
DOI：
10.1038/sj.onc.1201732
复制
发表时间：
1998-04-30
期刊：
影响因子：
8
通讯作者：
Bartholomew, C
中科院分区：
文献类型：
--
作者：
Kilbey, A;Bartholomew, C
Evi-1基因编码锌指转录抑制蛋白，其通常在发育中起作用，并且在髓性白血病中经常被激活，Evi-1具有两个不同的DNA结合结构域，ZF 1和ZF 2，以及一个确定的抑制结构域，但分子的其余部分的功能尚不清楚。ZF 2和阻遏物结构域已被证明是转化所需的，我们在这里表明，ZF 1也是必需的。Evi-1的可变剪接变体，命名为Delta 324，编码缺少部分ZF 1 DNA结合结构域和间插氨基酸239-514的蛋白质我们发现Delta 324既不能结合ZF 1，通过该位点抑制转录，也不能转化Rat 1成纤维细胞，重建研究表明，Delta 324中的缺陷通过重建ZF 1 DNA结合活性得到部分补充。然而，完整的功能还需要具有转录抑制活性的IR区域。因此，本研究表明，ZF 1，ZF 2和阻遏物结构域和IR区域都有助于Evi-1蛋白的转化效率。
The Evi-1 gene encodes a zinc finger transcriptional repressor protein that normally plays a role in development and is frequently activated in myeloid leukaemias, Evi-1 has two distinct DNA binding domains, ZF1 and ZF2, and a defined repressor domain but the function of the remainder of the molecule is unknown. The ZF2 and repressor domains have been shown to be required for transformation and we show here that ZF1 is also required. An alternative splice variant of Evi-1, designated Delta 324, encodes a protein which lacks a portion of the ZF1 DNA binding domain and the intervening amino acids 239-514 (designated IR) located between ZF1 and the repressor domain, We show that Delta 324 can neither bind ZF1, repress transcription through this site nor transform Rat1 fibroblasts, Reconstitution studies demonstrate that the defect in Delta 324 is partially complemented by recreating the ZF1 DNA binding activity. However, full function also requires the IR region which has transcriptional repressor activity. This study shows therefore, that ZF1, ZF2 and repressor domains and the IR region all contribute to the transformation efficiency of the Evi-1 protein.