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猬抑制因子在干细胞命运决定中的应用。

Application of porcupine inhibitors in stem cell fate determination.

机构信息

Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Chem Biol Drug Des. 2020 Oct;96(4):1052-1068. doi: 10.1111/cbdd.13704. Epub 2020 Jun 20.

Abstract

Porcupine (Porcn), a membrane-bound O-acyltransferase, is an endoplasmic reticulum-located protein that has catalytic activity. Porcn is involved in post-translational lipid modification of wingless-Int (Wnt) proteins and serves as an indispensable step in the Wnt proper secretion and signaling. Small-molecule inhibitors targeting Porcn catalytic function in vitro and in vivo are of great interest not only for treating cancer and fibrotic disorders but also in the field of regenerative medicine. Although a number of studies have been conducted, the exact role of Porcn in stem cell fate is not entirely clear. In some cases, Porcn inhibition declined differentiation rate, and in others, it induced stem cell differentiation toward specific lineages. In this review, we first elaborated the Porcn catalytic activity and its inhibitors. Then, we discussed about the recently reported results of Porcn inhibitors in stem cells self-renewal and differentiation.

摘要

猬(Porcn)是一种膜结合的 O-酰基转移酶,是一种位于内质网的具有催化活性的蛋白质。Porcn 参与了 Wnt 蛋白的翻译后脂质修饰,是 Wnt 蛋白正确分泌和信号传递所必需的步骤。针对 Porcn 催化功能的小分子抑制剂不仅在治疗癌症和纤维性疾病方面具有重要意义,而且在再生医学领域也备受关注。尽管已经进行了许多研究,但 Porcn 在干细胞命运中的确切作用尚不完全清楚。在某些情况下,Porcn 抑制会降低分化率,而在其他情况下,它会诱导干细胞向特定谱系分化。在这篇综述中,我们首先详细阐述了 Porcn 的催化活性及其抑制剂。然后,我们讨论了最近报道的 Porcn 抑制剂在干细胞自我更新和分化中的作用。

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