Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins
Specific Pax-6/microphthalmia transcription factor interactions involve their DNA-binding domains and inhibit transcriptional properties of both proteins
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DOI：
10.1074/jbc.m101812200
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发表时间：
2001-08-03
影响因子：
4.8
通讯作者：
Saule, S
中科院分区：
文献类型：
--
作者：
Planque, N;Leconte, L;Saule, S
Pax-6 和小眼转录因子 (Mitf) 是眼睛正常发育所必需的。 Pax-6 在神经视网膜和色素视网膜中表达，具有两个 DNA 结合域：配对域和同源域。 Pax-6 突变纯合小鼠无眼。 Mitf 是一种与色素沉着的发生和维持相关的碱性螺旋-环-螺旋亮氨酸拉链 (b-HLH-LZ) 转录因子，可识别眼睛发育过程中的视网膜色素上皮。 Mitf 功能的丧失导致异位神经视网膜的形成，而损害了背侧视网膜色素上皮。在本研究中，我们研究了 Pax-6 和 Mitf 之间的相互作用。在瞬时转染表达实验中，我们发现Pax-6和Mitf对其各自靶启动子的反式激活作用被两种转录因子的共转染强烈抑制。这种抑制是由于涉及 Pax-6 DNA 结合域和 Mitf b-HLH-LZ 域的直接蛋白质/蛋白质相互作用所致。这些结果表明 Pax-6/Mitf 相互作用可能对视网膜色素上皮的发育至关重要。
Pax-6 and microphthalmia transcription factor (Mitf) are required for proper eye development. Pax-6, expressed in both the neuroretina and pigmented retina, has two DNA-binding domains: the paired domain and the homeodomain. Mice homozygous for Pax-6 mutations are anophthalmic. Mitf, a basic helix-loop-helix leucine zipper (b-HLH-LZ) transcription factor associated with the onset and maintenance of pigmentation, identifies the retinal pigmented epithelium during eye development. Loss of Mitf function results in the formation of an ectopic neuroretina at the expense of the dorsal retinal pigmented epithelium. In the present study, we investigated the interaction between Pax-6 and Mitf. In transient transfection-expression experiments, we found that transactivating effects of Pax-6 and Mitf on their respective target promoters were strongly inhibited by co-transfection of both transcription factors. This repression was due to direct protein/protein interactions involving both Pax-6 DNA-binding domains and the Mitf b-HLH-LZ domain. These results suggest that Pax-6/Mitf interactions may be critical for retinal pigmented epithelium development.