Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation
Aurora kinase A-mediated phosphorylation of mPOU at a specific site drives skeletal muscle differentiation
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极光激酶 A 介导的 mPOU 在特定位点的磷酸化驱动骨骼肌分化
DOI：
10.1093/jb/mvz088
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kundu Tapas K
中科院分区：
文献类型：
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作者：
Karthigeyan Dhanasekan;Bose Arnab;Boopathi Ramachandran;Rao Vinay Jaya;Shima Hiroki;Bharathy Narendra;Igarashi Kazuhiko;Taneja Reshma;Trivedi Arun Kumar;Kundu Tapas K
极光激酶是丝氨酸/丝氨酸定向蛋白激酶，在有丝分裂中起关键作用。最近的证据强调了这些激酶在包括骨骼肌分化在内的多种生物学事件中的重要性。我们早期的研究发现转录因子POU6F1（或mPOU）是一种新的极光激酶（Aurk） a底物。在这里，我们报道极光激酶A磷酸化mPOU的Ser197并抑制其dna结合能力。深入研究mPOU的生理学，我们发现磷酸化-模拟（S197D） mPOU突变体在C2C12成肌细胞分化中表现出增强，而野生型或缺磷突变体在C2C12成肌细胞分化中表现出迟缓。有趣的是，在分化背景下，POU6F1耗竭表型会导致S197D-mPOU过表达。总之，我们的研究结果表明mPOU是骨骼肌分化的负调节因子，并强化了AurkA在骨骼肌形成中的重要性。
Aurora kinases are Ser/Thr-directed protein kinases which play pivotal roles in mitosis. Recent evidences highlight the importance of these kinases in multiple biological events including skeletal muscle differentiation. Our earlier study identified the transcription factor POU6F1 (or mPOU) as a novel Aurora kinase (Aurk) A substrate. Here, we report that Aurora kinase A phosphorylates mPOU at Ser197 and inhibit its DNA-binding ability. Delving into mPOU physiology, we find that the phospho-mimic (S197D) mPOU mutant exhibits enhancement, while the wild type or the phospho-deficient mutant shows retardation in C2C12 myoblast differentiation. Interestingly, POU6F1 depletion phenocopies S197D-mPOU overexpression in the differentiation context. Collectively, our results signify mPOU as a negative regulator of skeletal muscle differentiation and strengthen the importance of AurkA in skeletal myogenesis.