The role of LANP and ataxin 1 in E4F-mediated transcriptional repression
The role of LANP and ataxin 1 in E4F-mediated transcriptional repression
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DOI：
10.1038/sj.embor.7400983
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发表时间：
2007-07-01
期刊：
影响因子：
7.7
通讯作者：
Opal, Puneet
中科院分区：
文献类型：
--
作者：
Cvetanovic, Marija;Rooney, Robert J.;Opal, Puneet
富含亮氨酸的酸性核蛋白（LANP）属于抑制组蛋白乙酰转移酶的INHAT家族。LANP限制其抑制特定基因的机制尚不清楚。在这里，我们报道LANP与转录抑制因子E4F形成复合物并调节其活性。由于LANP与在神经退行性疾病脊髓小脑性共济失调1型（SCA1）中突变的ataxin 1-a蛋白相互作用，我们测试了ataxin 1是否可以改变E4F-LANP相互作用。我们发现，通过与E4F竞争LANP， ataxin 1减轻了LANP-E4F复合物诱导的转录抑制。据我们所知，这些结果提供了LANP和ataxin 1之间的第一个功能联系，并指出了SCA1中观察到的转录畸变的潜在机制。
The leucine-rich acidic nuclear protein (LANP) belongs to the INHAT family of corepressors that inhibits histone acetyltrans-ferases. The mechanism by which LANP restricts its repression to specific genes is unknown. Here, we report that LANP forms a complex with transcriptional repressor E4F and modulates its activity. As LANP interacts with ataxin 1-a protein mutated in the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1)-we tested whether ataxin 1 can alter the E4F-LANP interaction. We show that ataxin 1 relieves the transcriptional repression induced by the LANP-E4F complex by competing with E4F for LANP. These results provide the first functional link, to our knowledge, between LANP and ataxin 1, and indicate a potential mechanism for the transcriptional aberrations observed in SCA1.