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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.

DOI:10.1111/cbdd.13704
PMID:32419352
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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Application of porcupine inhibitors in stem cell fate determination.猬抑制因子在干细胞命运决定中的应用。
Chem Biol Drug Des. 2020 Oct;96(4):1052-1068. doi: 10.1111/cbdd.13704. Epub 2020 Jun 20.
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Identification of key residues and regions important for porcupine-mediated Wnt acylation.鉴定对刺猬蛋白介导的Wnt酰化起重要作用的关键残基和区域。
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reconstitution of Wnt acylation reveals structural determinants of substrate recognition by the acyltransferase human Porcupine.Wnt 酰化重建揭示了酰基转移酶人刺猬识别底物的结构决定因素。
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An fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase Porcupine.一项脂肪酰化分析揭示了酰基转移酶豪猪蛋白识别Wnt的机制。
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The porcupine inhibitor WNT974 provokes ectodermal lineage differentiation of human embryonic stem cells.猬抑制蛋白 WNT974 可诱导人胚胎干细胞向外胚层谱系分化。
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Stereoselective fatty acylation is essential for the release of lipidated WNT proteins from the acyltransferase Porcupine (PORCN).立体选择性脂肪酸酰化对于 Porcupine(PORCN)酰基转移酶释放脂质化 WNT 蛋白是必不可少的。
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Wnt family member 4 (WNT4) and WNT3A activate cell-autonomous Wnt signaling independent of porcupine acyltransferase or Wnt secretion.Wnt 家族成员 4(WNT4)和 WNT3A 独立于刺猬酰基转移酶或 Wnt 分泌激活细胞自主 Wnt 信号。
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Determination of the membrane topology of PORCN, an O-acyl transferase that modifies Wnt signalling proteins.确定 PORCN 的膜拓扑结构,PORCN 是一种酰基转移酶,可修饰 Wnt 信号蛋白。
Open Biol. 2021 Jun;11(6):200400. doi: 10.1098/rsob.200400. Epub 2021 Jun 30.

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