Smad regulation in TGF-beta signal transduction.
Smad regulation in TGF-beta signal transduction.
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DOI：
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发表时间：
2001-12
影响因子：
4
通讯作者：
A. Moustakas;S. Souchelnytskyi;C. Heldin
中科院分区：
文献类型：
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作者：
A. Moustakas;S. Souchelnytskyi;C. Heldin
Smad蛋白从转化生长因子-β（TGF-β）超家族配体传递信号，所述超家族配体通过受体丝氨酸/苏氨酸激酶的活化来调节细胞增殖、分化和死亡。受体激活的Smads（R-Smads）的磷酸化导致与共同介质Smad（Co-Smad）形成复合物，其被输入到细胞核。核Smad寡聚体与DNA结合并与转录因子结合以调节靶基因的表达。或者，核R-Smads与泛素连接酶结合并促进转录抑制因子的降解，从而促进TGF-β对靶基因的调控。Smads本身也可以被泛素化并被蛋白酶体降解。最后，抑制性Smads（I-Smads）阻断受体对R-Smads的磷酸化，并促进受体复合物的泛素化和降解，从而抑制信号传导。
Smad proteins transduce signals from transforming growth factor-beta (TGF-beta) superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. Phosphorylation of receptor-activated Smads (R-Smads) leads to formation of complexes with the common mediator Smad (Co-Smad), which are imported to the nucleus. Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes. Alternatively, nuclear R-Smads associate with ubiquitin ligases and promote degradation of transcriptional repressors, thus facilitating target gene regulation by TGF-beta. Smads themselves can also become ubiquitinated and are degraded by proteasomes. Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling.