Çizmecioğlu Onur
Department of Molecular Biology and Genetics, Science Faculty, İhsan Doğramacı Bilkent University, Ankara, Turkey.
Turk J Biol. 2022 Feb 8;46(3):207-215. doi: 10.55730/1300-0152.2609. eCollection 2022.
Phosphoinositide 3-kinase (PI3K) signaling pathway is essential for normal physiology and is impaired in diseases such as premalignant hyperproliferative disorders, primary immunodeficiency, metabolic disorders, and cancer. Although the core PI3K pathway components are known today, a long-standing gap in our knowledge of PI3K signaling concerns how distinct PI3K isoforms and their activity patterns contribute to the functional consequences of pathway upregulation. In order to address this issue, we devised a molecular genetic cell model, which allowed temporal regulation of the indispensable PI3K isoform, p110α in distinct stages of the cell cycle. We found that late M and early G1 presence of p110α is key for proper cell cycle progression, whereas its S-phase abundance was redundant. Our results also emphasize a critical dependence of cell cycle reentry on early G1 activity of p110α. Collectively, our findings provide a temporal perspective to p110α activation and offer insight into which wave of PI3K activity could be essential for cell cycle progression.
磷酸肌醇-3激酶（PI3K）信号通路对正常生理功能至关重要，而在诸如癌前增生性疾病、原发性免疫缺陷、代谢紊乱和癌症等疾病中会受损。尽管如今已知PI3K信号通路的核心组成部分，但我们对PI3K信号传导的长期认知空白在于不同的PI3K亚型及其活性模式如何导致通路上调的功能后果。为了解决这个问题，我们设计了一种分子遗传细胞模型，该模型能够在细胞周期的不同阶段对不可或缺的PI3K亚型p110α进行时间调控。我们发现，p110α在M期末期和G1早期的存在是细胞周期正常进展的关键，而其在S期的丰度则是多余的。我们的结果还强调了细胞周期重新进入对p110α早期G1活性的关键依赖性。总体而言，我们的研究结果为p110α激活提供了一个时间视角，并深入了解了哪一波PI3K活性可能对细胞周期进展至关重要。
