p110α activity at the M-to-G1 transition is critical for cellular proliferation and renntry into the cell cycle

Date
2022-06-14
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Source Title
Turkish Journal of Biology
Print ISSN
13000152
Electronic ISSN
Publisher
TUBITAK
Volume
46
Issue
3
Pages
207 - 215
Language
English
Type
Article
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Abstract

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.

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Keywords
Cell cycle, Signal transduction, Phosphoinositide 3-kinase pathway, Temporal regulation, p110α
Citation
Published Version (Please cite this version)