Key role for ubiquitin protein modification in TGFβ signal transduction.
Key role for ubiquitin protein modification in TGFβ signal transduction.
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DOI：
10.3109/03009734.2012.654858
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发表时间：
2012-05
影响因子：
3.4
通讯作者：
ten Dijke P
中科院分区：
文献类型：
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作者：
De Boeck M;ten Dijke P
转化生长因子β（transforming growth factor β，TGFβ）超家族的信号转导分子在细胞行为调控中起着至关重要的作用。TGFβ通过Smad蛋白调节基因转录，并通过非Smad途径进行信号传导。TGFβ途径受到严格调节，扰动导致肿瘤发生。已知几种途径组分通过E3连接酶的泛素化被靶向用于蛋白酶体降解。Smurfs是众所周知的TGFβ负调节因子，其作为E3连接酶起作用，由衔接子如I-Smads募集。TGFβ信号传导也可以通过E3连接酶如Arkadia增强，其靶向阻遏物以进行降解。越来越清楚的是，E3连接酶通常靶向多个途径，从而充当信号传导串扰的介体。通过泛素化的调节涉及E3连接酶，衔接蛋白和去泛素化酶（DUB）的复杂网络，后者通过从其靶点去除泛素起作用。有趣的是，已知非降解性泛素修饰也在TGFβ信号传导中发挥重要作用。因此，泛素修饰在TGFβ信号转导中起着关键作用，在这篇综述中，我们提供了已知球员的概述，重点是最近的进展。
The transforming growth factor β (TGFβ) superfamily of signal transduction molecules plays crucial roles in the regulation of cell behavior. TGFβ regulates gene transcription through Smad proteins and signals via non-Smad pathways. The TGFβ pathway is strictly regulated, and perturbations lead to tumorigenesis. Several pathway components are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. Smurfs are well known negative regulators of TGFβ, which function as E3 ligases recruited by adaptors such as I-Smads. TGFβ signaling can also be enhanced by E3 ligases, such as Arkadia, that target repressors for degradation. It is becoming clear that E3 ligases often target multiple pathways, thereby acting as mediators of signaling cross-talk. Regulation via ubiquitination involves a complex network of E3 ligases, adaptor proteins, and deubiquitinating enzymes (DUBs), the last-mentioned acting by removing ubiquitin from its targets. Interestingly, also non-degradative ubiquitin modifications are known to play important roles in TGFβ signaling. Ubiquitin modifications thus play a key role in TGFβ signal transduction, and in this review we provide an overview of known players, focusing on recent advances.