Wogonoside induces depalmitoylation and translocation of PLSCR1 and N-RAS in primary acute myeloid leukaemia cells.
Wogonoside induces depalmitoylation and translocation of PLSCR1 and N-RAS in primary acute myeloid leukaemia cells.
复制标题
汉黄芩苷诱导原发性急性髓系白血病细胞中 PLSCR1 和 N-RAS 的去棕榈酰化和易位
DOI：
10.1111/jcmm.13481
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发表时间：
2018-04
影响因子：
5.3
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Li H;Yu X;Liu X;Hu P;Shen L;Zhou Y;Zhu Y;Li Z;Hui H;Guo Q;Xu J
急性髓性白血病（AML）包括一系列不同的遗传亚型，涉及复杂的基因突变和特定的分子改变。特定蛋白的翻译后修饰影响其易位、稳定性、聚集甚至导致疾病进展。针对癌细胞中特定蛋白质的翻译后修饰的治疗方法代表了一种新的治疗策略。PLSCR1的非均匀亚细胞分布参与了原发性AML细胞分化。然而，PLSCR1的核易位机制尚不清楚。在这里，我们利用观察结果，在一些原发性AML细胞中，尽管遗传异质性导致PLSCR1通过酰基蛋白硫酯酶1 (APT‐1)（一种催化蛋白去棕榈酰化的酶）进行去棕榈酰化，但在皂荚皂苷治疗期间，PLSCR1的核易位可能被诱导。此外，我们在另一种AML相关蛋白N - RAS上发现了类似的现象。Wogonoside抑制小GTPase N - RAS的棕榈酰化，并增强其向高尔基复合物的运输，导致一些原发性AML细胞中N - RAS/RAF1通路失活。综上所述，我们的研究结果为wogono苷诱导PLSCR1核易位的机制提供了新的见解，并阐明了AML中N - RAS去棕榈酰化对其高尔基转运和RAF1信号失活的影响。
Acute myeloid leukaemia (AML) comprises a range of disparate genetic subtypes, involving complex gene mutations and specific molecular alterations. Post‐translational modifications of specific proteins influence their translocation, stability, aggregation and even leading disease progression. Therapies that target to post‐translational modification of specific proteins in cancer cells represent a novel treatment strategy. Non‐homogenous subcellular distribution of PLSCR1 is involved in the primary AML cell differentiation. However, the nuclear translocation mechanism of PLSCR1 remains poorly understood. Here, we leveraged the observation that nuclear translocation of PLSCR1 could be induced during wogonoside treatment in some primary AML cells, despite their genetic heterogeneity that contributed to the depalmitoylation of PLSCR1 via acyl protein thioesterase 1 (APT‐1), an enzyme catalysing protein depalmitoylation. Besides, we found a similar phenomenon on another AML‐related protein, N‐RAS. Wogonoside inhibited the palmitoylation of small GTPase N‐RAS and enhanced its trafficking into Golgi complex, leading to the inactivation of N‐RAS/RAF1 pathway in some primary AML cells. Taken together, our findings provide new insight into the mechanism of wogonoside‐induced nuclear translocation of PLSCR1 and illuminate the influence of N‐RAS depalmitoylation on its Golgi trafficking and RAF1 signalling inactivation in AML.
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DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Agudo-Ibanez, Lorena;Herrero, Ana;Crespo, Piero
通讯作者：
Crespo, Piero
影响因子：
20.3
作者：
Chen, Yan;Hui, Hui;Guo, Qinglong
通讯作者：
Guo, Qinglong
影响因子：
20.3
作者：
Bowen, DT;Frew, ME;Linch, DC
通讯作者：
Linch, DC
影响因子：
7.3
作者：
Lorentzen, Anna;Kinkhabwala, Ali;Bastiaens, Philippe I. H.
通讯作者：
Bastiaens, Philippe I. H.