The transcriptional role of Smads and FAST (FoxH1) in TGFβ and activin signalling
The transcriptional role of Smads and FAST (FoxH1) in TGFβ and activin signalling
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DOI：
10.1016/s0303-7207(01)00524-x
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发表时间：
2001-06-30
影响因子：
4.1
通讯作者：
Labbé, E
中科院分区：
文献类型：
--
作者：
Attisano, L;Silvestri, C;Labbé, E
Smad蛋白家族是TGF β超家族信号通路的关键组分。配体添加诱导特异性受体调节的Smads的磷酸化。然后与共同的介体Smad 4形成异聚复合物。然后，该复合物从细胞质易位到细胞核中。一旦到达那里，R-Smad/Smad 4复合物就会与多种DNA结合蛋白相互作用，从而靶向多种已消失的启动子。然后，含有Smad的DNA结合复合物可以通过募集共激活子和共抑制子来正向或负向调节基因表达。Xenopus FAST（现在称为FoxH 1）是第一个被鉴定的Smad DNA结合伴侣，FoxH 1家族现在包括来自小鼠，人类和斑马鱼的相关蛋白质。在所有检测的生物体中，FoxH 1主要在发育的最早阶段表达，因此FoxH 1被认为在这些早期发育阶段介导TGF β超家族信号中起关键作用。其他Smad伴侣的范围从那些普遍表达的伴侣到仅存在于特定细胞类型或发育阶段的其他伴侣。因此，Smads与广泛的特异性转录伴侣的相互作用对于产生对TGF β超家族成员的多种生物反应是重要的。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
The Smad family of proteins are critical components of the TGF beta superfamily signalling pathway. Ligand addition induces phosphorylation of specific receptor-regulated Smads. which then form heteromeric complexes with the common mediator Smad, Smad4. This complex then translocates from the cytoplasm into the nucleus. Once there, the R-Smad/Smad4 complex interacts with a variety of DNA binding proteins and is thereby targetted to a diverse array of gone promoters. The Smad-containing DNA binding complex can then positively or negatively regulate gene expression through the recruitment of co-activators and co-repressors. Xenopus FAST (now known as FoxH1) was the first Smad DNA binding partner identified and the FoxH1 family now includes related proteins from mouse, human and Zebrafish. In all organisms examined, FoxH1 is expressed primarily during the earliest stages of development and thus FoxH1 is thought to play a critical role in mediating TGF beta superfamily signals during these early developmental stages. Other Smad partners range from those that are ubiquitously expressed to others that are present only in specific cell types or developmental stages. Thus, it is the interaction of Smads with a wide range of specific transcriptional partners that is important for the generation of diverse biological responses to TGF beta superfamily members. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.