Drosophila distal-less negatively regulates dDREF by inhibiting its DNA binding activity
Drosophila distal-less negatively regulates dDREF by inhibiting its DNA binding activity
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DOI：
10.1016/j.bbaexp.2006.07.002
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Yamaguchi, Masamitsu
中科院分区：
文献类型：
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作者：
Hayashi, Yuko;Kato, Masaki;Yamaguchi, Masamitsu
果蝇DNA复制相关元件结合因子（dDREF）是许多携带DRE序列5'- tatgata的增殖相关基因表达所必需的。dDREF在眼显像盘中的过度表达可诱导异位DNA合成、细胞凋亡和光感受器细胞特异性抑制，导致成人眼睛表型粗糙。在本研究中，远端缺失基因（Dll）减少一半的剂量增强了dDREF诱导的粗糙眼表型，提示Dll负向调节dDREF在眼成像盘细胞中的活性。生化分析显示Dll的n端（30aa ~ 124aa）和c端（190aa ~ 327aa）区域与dDREF的DNA结合域（16aa ~ 125aa）相互作用，但目前尚不清楚这种相互作用是直接的还是间接的。电泳迁移率转移实验表明，Dll因此抑制DNA结合。同源结构域蛋白Dll对ddref功能的抑制可能有助于在发育过程中分化偶联抑制细胞增殖。(c) 2006 Elsevier B.V.版权所有
The Drosophila DNA replication-related element binding factor (dDREF) is required for expression of many proliferation-related genes carrying the DRE sequence, 5'-TATCGATA. Over-expression of dDREF in the eye imaginal disc induces ectopic DNA synthesis, apoptosis and inhibition of photoreceptor cell specification, and results in rough eye phenotype in adults. In the present study, half dose reduction of the Distal-less (Dll) gene enhanced the dDREF-induced rough eye phenotype, suggesting that Dll negatively regulates dDREF activity in eye imaginal disc cells. Biochemical analyses revealed the N-terminal (30aa to 124aa) and C-terminal (190aa to 327aa) regions of Dll to interact with the DNA binding domain (16aa to 125aa) of dDREF, although it is not clear yet whether the interaction is direct or indirect. Electrophoretic mobility shift assays showed that Dll thereby inhibits DNA binding. The repression of this dDREF-function by a homeodomain protein like Dll may contribute to the differentiation-coupled repression of cell proliferation during development. (c) 2006 Elsevier B.V. All rights reserved.