Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
Stem Cell Res Ther. 2020 Jun 18;11(1):243. doi: 10.1186/s13287-020-01766-9.
In our previous study, a venom-based peptide named Gonearrestide (also named P13) was identified and demonstrated with an effective inhibition in the proliferation of colon cancer cells. In this study, we explored if P13 and its potent mutant M6 could promote the proliferation of human embryonic stem cells and even maintain their self-renewal.
The structure-function relationship analysis on P13 and its potent mutant M6 were explored from the molecular mechanism of corresponding receptor activation by a series of inhibitor assay plus molecular and dynamics simulation studies.
An interesting phenomenon is that P13 (and its potent mutant M6), an 18AA short peptide, can activate both FGF and TGFβ signaling pathways. We demonstrated that the underlying molecular mechanisms of P13 and M6 could cooperate with proteoglycans to complete the "dimerization" of FGFR and TGFβ receptors.
Taken together, this study is the first research finding on a venom-based peptide that works on the FGF and TGF-β signaling pathways to maintain the self-renewal of hESCs.
在我们之前的研究中，发现了一种基于毒液的肽，名为 Gonearrestide（也称为 P13），它能有效抑制结肠癌细胞的增殖。在这项研究中，我们探讨了 P13 及其强效突变体 M6 是否能促进人胚胎干细胞的增殖，甚至维持其自我更新。
通过一系列抑制剂检测加上分子和动力学模拟研究，从相应受体激活的分子机制方面探讨了 P13 及其强效突变体 M6 的结构-功能关系。
一个有趣的现象是，P13（及其强效突变体 M6）是一个 18 个氨基酸的短肽，能够激活 FGF 和 TGFβ 信号通路。我们证明了 P13 和 M6 的潜在分子机制可以与蛋白聚糖一起完成 FGFR 和 TGFβ 受体的“二聚化”。
总之，这项研究首次发现一种基于毒液的肽可以作用于 FGF 和 TGF-β 信号通路来维持 hESC 的自我更新。
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