Biological roles and mechanistic actions of co-repressor complexes.
Biological roles and mechanistic actions of co-repressor complexes.
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发表时间：
2002-02
影响因子：
4
通讯作者：
Kristen Jepsen;M. Rosenfeld
中科院分区：
文献类型：
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作者：
Kristen Jepsen;M. Rosenfeld
转录抑制在多种生物学过程中起着至关重要的作用，部分由非DNA结合的辅助抑制因子介导。密切相关的辅阻遏蛋白N-CoR和SMRT，虽然最初是根据它们通过核受体与转录阻遏相关并赋予转录阻遏的能力而鉴定的，但已显示被招募到许多类别的转录因子中，并且实际上是含有组蛋白脱乙酰酶蛋白的多种蛋白质复合物的组分。这种与组蛋白脱乙酰酶活性的关联提供了允许DNA结合蛋白与N-CoR或SMRT相互作用以抑制特定靶基因转录的机制的重要组成部分。N-CoR和SMRT都是细胞信号通路的重要靶点，影响其表达水平、亚细胞定位以及与其他蛋白的结合。最近，这些蛋白质的生物学重要性已经通过对基因工程小鼠和人类疾病如急性早幼粒细胞白血病（APL）和甲状腺激素抵抗（RTH）的研究而被揭示。
Transcriptional repression, which plays a crucial role in diverse biological processes, is mediated in part by non-DNA-binding co-repressors. The closely related co-repressor proteins N-CoR and SMRT, although originally identified on the basis of their ability to associate with and confer transcriptional repression through nuclear receptors, have been shown to be recruited to many classes of transcription factor and are in fact components of multiple protein complexes containing histone deacetylase proteins. This association with histone deacetylase activity provides an important component of the mechanism that allows DNA-binding proteins interacting with N-CoR or SMRT to repress transcription of specific target genes. Both N-CoR and SMRT are important targets for cell signaling pathways, which influence their expression levels, subcellular localization and association with other proteins. Recently, the biological importance of these proteins has been revealed by studies of genetically engineered mice and human diseases such as acute promyelocytic leukemia (APL) and resistance to thyroid hormone (RTH).