Groucho-dependent and -independent repression activities of runt domain proteins
Groucho-dependent and -independent repression activities of runt domain proteins
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DOI：
10.1128/mcb.17.9.5581
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发表时间：
1997-09-01
影响因子：
5.3
通讯作者：
Gergen, JP
中科院分区：
文献类型：
--
作者：
Aronson, BD;Fisher, AL;Gergen, JP
Runt结构域蛋白是一种转录调节因子，它可以为从昆虫的模式形成到人类白血病发生的过程指定细胞命运。Runt结构域家族成员是基于128个氨基酸的Runt结构域的存在来定义的，这对于序列特异性DNA结合是必要的和足够的。我们证明了一个进化保守的蛋白质-蛋白质之间的相互作用Runt结构域蛋白和辅阻遏物Groucho。然而，相互作用是独立的Runt结构域，可以映射到一个5-氨基酸序列，VWRPY，目前在C末端的所有Runt结构域蛋白。果蝇Runt和Groucho基因相互作用;在体内抑制的一个子集的Runt调节基因依赖于与Groucho的相互作用，是敏感的Groucho剂量。Runt对一个基因的抑制是独立于VWRPY和Groucho的，因此证明了Runt结构域蛋白抑制的替代机制。与其他与Groucho相互作用的转录调节蛋白不同，Runt结构域蛋白已知激活转录。这表明Runt结构域蛋白-Groucho相互作用可能受到调节。
Runt domain proteins are transcriptional regulators that specify cell fates for processes extending from pattern formation in insects to leukemogenesis in humans. Runt domain family members are defined based on the presence of the 128-amino-acid Runt domain, which is necessary and sufficient for sequence-specific DNA binding. We demonstrate an evolutionarily conserved protein-protein interaction between Runt domain proteins and the corepressor Groucho. The interaction, however, is independent of the Runt domain and can be mapped to a 5-amino-acid sequence, VWRPY, present at the C terminus of all Runt domain proteins. Drosophila melanogaster Runt and Groucho interact genetically; the in vivo repression of a subset of Runt-regulated genes is dependent on the interaction with Groucho and is sensitive to Groucho dosage. Runt's repression of one gene, engrailed, is independent of VWRPY and Groucho, thus demonstrating alternative mechanisms for repression by Runt domain proteins. Unlike other transcriptional regulatory proteins that interact with Groucho, Runt domain proteins are known to activate transcription. This suggests that the Runt domain protein-Groucho interaction may he regulated.