Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins.
Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins.
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DOI：
10.1016/j.celrep.2013.08.027
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发表时间：
2013-09-26
期刊：
影响因子：
8.8
通讯作者：
Resh MD
中科院分区：
文献类型：
--
作者：
Rios-Esteves J;Resh MD
Wnt蛋白含有一种不寻常的脂质修饰，棕榈油酸。活性Wnt信号的产生需要酰基转移酶Porcupine，并且依赖于棕榈油酸与Wnt的连接。这种单不饱和脂肪酸的来源尚未确定，也不知道豪猪如何识别其底物，以及去饱和是否发生在脂肪酸转移到Wnt之前或之后。在这里，我们表明，硬脂酰去饱和酶（SCD）产生的单不饱和脂肪酸底物，然后转移豪猪Wnt。用SCD抑制剂处理细胞阻断了棕榈酸酯类似物掺入Wnt3a和Wnt5a中，并减少了Wnt分泌以及自分泌和旁分泌Wnt信号传导。SCD抑制剂的效果被拯救的外源性添加单不饱和脂肪酸。我们认为SCD是Wnt生物合成和加工的关键分子，SCD抑制为阻断Wnt通路激活提供了另一种机制。
Wnt proteins contain an unusual lipid modification, palmitoleic acid. Production of an active Wnt signal requires the acyltransferase Porcupine and depends on attachment of palmitoleic acid to Wnt. The source of this monounsaturated fatty acid has not been identified, and it is not known how Porcupine recognizes its substrate and whether desaturation occurs before or after fatty acid transfer to Wnt. Here we show that stearoyl desaturase (SCD) generates a monounsaturated fatty acid substrate which is then transferred by Porcupine to Wnt. Treatment of cells with SCD inhibitors blocked incorporation of palmitate analogs into Wnt3a and Wnt5a, and reduced Wnt secretion as well as autocrine and paracrine Wnt signaling. The SCD inhibitor effects were rescued by exogenous addition of monounsaturated fatty acids. We propose that SCD is a key molecular player responsible for Wnt biogenesis and processing and that SCD inhibition provides an alternative mechanism for blocking Wnt pathway activation.
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DOI：
10.1074/jbc.m112.381970
发表时间：
2012-10-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Proffitt KD;Virshup DM
通讯作者：
Virshup DM
影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
4.1
作者：
Kurayoshi, Manabu;Yamamoto, Hideki;Kikuchi, Akira
通讯作者：
Kikuchi, Akira
影响因子：
2.7
作者：
Herr, Patrick;Basler, Konrad
通讯作者：
Basler, Konrad
影响因子：
4.8
作者：
Liang, XQ;Lu, Y;Resh, MD
通讯作者：
Resh, MD