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MOL CELL：新型胆固醇共价修饰蛋白是hedgehog信号通路必须组分

2017-03-25 MedSci MedSci原创

胆固醇共价修饰蛋白Hedgehog信号通路
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研究人员组构建了SMO-D99N（人源SMO中的D95N）的Knock-In小鼠。发现纯合的SmoD99N/D99N小鼠会造成胚胎致死（下图）。病理学研究表明，纯合SmoD99N/D99N小鼠出现了严重的胚胎和心脏发育障碍。并且小鼠的神经管中Hh下游基因的表达也显著降低。进一步的定量PCR进一步确认了Hh pathway下游基因表达的抑制。

最近，来自武汉大学生命科学学院的研究人员报道了一项关于胆固醇共价修饰蛋白Smoothened (SMO)的研究， 相关研究刊登于国际杂志MOL CELL上。

Hedgehog信号通路是调节动物胚胎发育的经典信号通路之一，Hedgehog(HH) 基因是1980年由 Nusslein-Vollhard 和Wieschaus 在研究果蝇的突变体时发现 ，该基因突变会导致果蝇幼虫体表出现许多刺突，形似刺猬，故命名为 Hedgehog。

研究人员组构建了SMO-D99N（人源SMO中的D95N）的Knock-In小鼠。发现纯合的SmoD99N/D99N小鼠会造成胚胎致死（下图）。病理学研究表明，纯合SmoD99N/D99N小鼠出现了严重的胚胎和心脏发育障碍。并且小鼠的神经管中Hh下游基因的表达也显著降低。进一步的定量PCR进一步确认了Hh pathway下游基因表达的抑制。

研究表明SMO通过Asp95（D95）残基上的胆固醇共价修饰，SMO的胆固醇修饰被Ptch1抑制，并被Hh增强。同时，SMO胆固醇化对于Hh信号传导和胚胎发育至关重要。 胆固醇修饰对SMO的活化有重要意义，提示SMO的胆固醇修饰可以作为一个治疗Hh相关癌症的新靶点。

原始出处：

Xu Xiao, Jing-Jie Tang, Chao Peng, Wen-Wei Qiu. et al.Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling. Science  24 Mar 2017:Vol. 355, Issue 6331, pp. 1247-1248

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    2017-12-22 yibei

    #Hedgehog#

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    2018-02-13 zhaozhouchifen

    #Cell#

    0

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    2017-12-10 维他命

    #CEL#

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    2017-03-27 wgx310

    #信号通路#

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    2017-03-27 zhangyxzsh

    #修饰#

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