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Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling.
Trends in Biochemical Sciences ( IF 11.6 ) Pub Date : 2020-02-17 , DOI: 10.1016/j.tibs.2020.01.006
Xiaofeng Qi 1 , Xiaochun Li 2
Affiliation  

Cell differentiation and proliferation require Hedgehog (HH) signaling and aberrant HH signaling causes birth defects or cancers. In this signaling pathway, the N-terminally palmitoylated and C-terminally cholesterylated HH ligand is secreted into the extracellular space with help of the Dispatched-1 (DISP1) and Scube2 proteins. The Patched-1 (PTCH1) protein releases its inhibition of the oncoprotein Smoothened (SMO) after binding the HH ligand, triggering downstream signaling events. In this review, we discuss the recent structural and biochemical studies on four major components of the HH pathway: the HH ligand, DISP1, PTCH1, and SMO. This research provides mechanistic insights into how HH signaling is generated and transduced from the cell surface into the intercellular space and will aid in facilitating the treatment of HH-related diseases.

中文翻译:


对刺猬信号产生和转导的机制见解。



细胞分化和增殖需要 Hedgehog (HH) 信号传导,异常的 HH 信号传导会导致出生缺陷或癌症。在此信号通路中,N 端棕榈酰化和 C 端胆固醇化 HH 配体在 Dispatched-1 (DISP1) 和 Scube2 蛋白的帮助下分泌到细胞外空间。 Patched-1 (PTCH1) 蛋白在与 HH 配体结合后释放其对癌蛋白 Smoothened (SMO) 的抑制,从而触发下游信号事件。在这篇综述中,我们讨论了最近对 HH 通路的四个主要组成部分的结构和生化研究:HH 配体、DISP1、PTCH1 和 SMO。这项研究提供了关于 HH 信号如何产生并从细胞表面转导到细胞间隙的机制见解,并将有助于促进 HH 相关疾病的治疗。
更新日期:2020-02-17
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