发现癌症发展过程关键代谢的调控机制
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发现癌症发展过程关键代谢的调控机制


塞维利亚大学(Universidad de Sevilla)的研究人员参与的这项研究,旨在识别丙酮酸激酶(piruvato quinasa)这种对糖代谢至关重要、并与细胞增殖和生长密切相关的酶分子调控细节。

这些研究成果是塞维利亚大学伊雷内·迪亚斯·莫雷诺(Irene Díaz Moreno)教授的领导团队与本古里安大学埃亚尔·阿尔贝利( Eyal Arbely )教授团队之间的长期合作成果。最新研究成果已发表在美国国家科学院的科学期刊 《美国国家科学院院刊》(PNAS) 。

在这项研究中,科研人员展示了乙酰化这一可逆的化学修饰,作为一种精细的细胞调控机制如何影响丙酮酸激酶的动态和功能。在正常细胞中,这些化学标记能使细胞根据周围环境精确地进行调节代谢;然而,在癌症等病理情况下,失去这一调控机制可能会改变代谢流向,从而促进失控的细胞增殖。

“理解这些精确且细致地调控丙酮酸激酶功能的分子机制,有助于我们解读驱动癌细胞增殖的代谢变化。卡尔图哈岛科学研究中心(US–CSIC)的化学研究所 伊雷内·迪亚斯–莫雷诺(Irene Díaz-Moreno)教授 解释道。

丙酮酸激酶有两种变体:与成人组织相关的 PKM1,以及与成人和胚胎组织均相关的 PKM2;通过结合生化、生物物理、结构技术分析和计算机模拟等多种方法,研究人员证明,丙酮酸激酶在特定位置发生乙酰化会抑制酶的功能并降低其稳定性。此外,研究人员还发现某些乙酰化对不同变体(PKM1 和 PKM2)产生的影响方式不同,这揭示了它们各自特有的调控机制。

总的来说,这些研究发现有助于在分子层面理解这类关键代谢酶的调控方式,它们提供了重要信息,帮助我们解释其在特定情况下的功能行为,例如在癌症的环境下,对丙酮酸激酶的作用失去控制会促进细胞的快速增殖。

D. Pavlenko, J. Tamargo-Azpilicueta, H. Nudelman, Y. Ankri, A. Shahar, I. Díaz-Moreno & E. Arbely (2025). Isoform-specific regulation of PKM by acetylation. Proc. Natl. Acad. Sci. U.S.A. 122: e2527086122, DOI: 10.1073/pnas.2527086122
Regions: Europe, Spain
Keywords: Health, Well being

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