Coco is a dual activity modulator of TGFβ signaling
Coco is a dual activity modulator of TGFβ signaling
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DOI：
10.1242/dev.122358
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发表时间：
2015-08-01
期刊：
影响因子：
4.6
通讯作者：
Brivanlou, Ali H.
中科院分区：
文献类型：
--
作者：
Deglincerti, Alessia;Haremaki, Tomomi;Brivanlou, Ali H.
TGF β信号通路是发育过程和疾病的重要调节因子。TGF β配体的活性由干扰配体和受体之间相互作用的各种可溶性抑制剂家族调节。在一个无偏见的，全基因组RNAi筛选，以确定参与配体依赖性信号传导的基因，我们意外地确定了BMP/激活素/Nodal抑制剂可可作为TGF β 1信号传导的增强剂。可可在细胞培养物和爪蟾外植体中与TGF β 1协同作用。在分子上，Coco与TGF β 1结合，并增强TGF β 1与其受体Alk 5的结合。因此，可可既可以作为信号传导的抑制剂，也可以作为信号传导的增强剂，这取决于它所结合的配体。这一发现提出了全球重新考虑调节TGF β信号传导的分子机制的必要性。
The TGF beta signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGF beta ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGF beta 1 signaling. Coco synergizes with TGF beta 1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGF beta 1 and enhances TGF beta 1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGF beta signaling.