PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.
PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.
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DOI：
10.1038/s41467-022-32976-9
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发表时间：
2022-09-06
影响因子：
16.6
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中科院分区：
文献类型：
--
作者：
蛋白激酶介导的磷酸化在许多生物过程中起着关键作用。然而，关键调节激酶的鉴定仍然是一个巨大的挑战。在这里，我们开发了一种基于trans-omics的方法，中央激酶推理，通过整合定量转录组学和磷酸蛋白质组学数据来预测潜在的关键激酶。使用已知的与抗癌药物耐药性相关的激酶，我们的方法的准确性由曲线下面积表示，比激酶底物富集分析高5.2%至29.5%。我们进一步使用这种方法来分析trans-omic数据在肝细胞成熟和肝重编程的人皮肤成纤维细胞，发现5激酶作为调节剂在这两个过程中。进一步的实验表明，丝氨酸/苏氨酸激酶，PIM 1，促进肝转换和保护人类皮肤成纤维细胞从重编程诱导的铁凋亡和细胞周期停滞。这项研究不仅揭示了新的调节激酶，而且提供了一个有用的方法，可能会扩展到预测参与其他生物过程的中枢激酶。蛋白激酶介导的磷酸化在许多生物过程中起着关键作用。在本文中，作者开发了一种基于trans-omics的算法，称为Central Kinase Inference，以整合定量转录组学和磷酸化蛋白质组学数据，发现PIM 1通过抑制重编程诱导的铁凋亡和细胞周期停滞来促进肝脏转化。
Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two processes. Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes. Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.
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影响因子：
13.3
作者：
Chen, Lei-Lei;Wang, Yong-Bo;Xue, Yu
通讯作者：
Xue, Yu
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
定量磷酸蛋白质组学揭示金雀花素是三阴性乳腺癌细胞中细胞周期和 DNA 损伤反应途径的调节剂
影响因子：
5.2
作者：
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通讯作者：
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23.9
作者：
Gascon, Sergio;Murenu, Elisa;Goetz, Magdalena
通讯作者：
Goetz, Magdalena
影响因子：
16.6
作者：
Hogrebe A;von Stechow L;Bekker-Jensen DB;Weinert BT;Kelstrup CD;Olsen JV
通讯作者：
Olsen JV