Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase
Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase
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DOI：
10.1073/pnas.98.3.974
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发表时间：
2001-01-30
影响因子：
11.1
通讯作者：
Delynck, R
中科院分区：
文献类型：
--
作者：
Zhang, Y;Chang, CB;Delynck, R
Smad蛋白是转化生长因子-β超家族多肽生长因子的关键细胞内信号效应因子。在受体诱导激活之后，Smads进入细胞核，激活一组选定的靶基因的转录。Smad蛋白的活性必须受到严格的调控，才能及时发挥不同配体的生物学效应。在这里，我们报告了SMurf2的鉴定，它是E3泛素连接酶Hect家族的一个新成员。SMurf2选择性地与受体调节的Smads相互作用，并优先针对Smad1进行泛素化和蛋白酶体介导的降解。在较高的表达水平，S-2也会降低Smad2的蛋白水平，但不会降低Smad3的蛋白水平。在非洲爪哇胚胎中，异位表达的SMurf2特异性地抑制Smad1的反应，从而通过骨形态发生蛋白信号影响胚胎模式。这些发现表明，SMurf2可能通过与SMurf1相似但又独立的不同的降解途径来调节细胞对转化生长因子-β/骨形态发生蛋白信号的反应能力。
Smad proteins are key intracellular signaling effecters for the transforming growth factor-beta superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tightly regulated to exert the biological effects of different ligands in a timely manner. Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3. In Xenopus embryos, ectopic Smurf2 expression specifically inhibits Smad1 responses and thereby affects embryonic patterning by bone morphogenetic protein signals. These findings suggest that Smurf2 may regulate the competence of a cell to respond to transforming growth factor-beta /bone morphogenetic protein signaling through a distinct degradation pathway that is similar to, yet independent of, Smurf1.