The Role of Nuclear Phosphoinositides in the p53-MDM2 Nexus
Recent insights into the p53-MDM2 nexus have advanced deeper understanding of their regulation and potent impact on cancer heterogeneity. The roles of nuclear phosphoinositide (PIP<sub>n</sub>s) in modulating this pathway are emerging as a key mechanism. Here, we dissect the molecular me...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/15/1126 |
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| Summary: | Recent insights into the p53-MDM2 nexus have advanced deeper understanding of their regulation and potent impact on cancer heterogeneity. The roles of nuclear phosphoinositide (PIP<sub>n</sub>s) in modulating this pathway are emerging as a key mechanism. Here, we dissect the molecular mechanisms by which nuclear PIP<sub>n</sub>s stabilize p53 through the recruitment of small heat shock proteins (sHSPs), activate the nuclear phosphatidylinositol 3-kinase (PI3K)-AKT signaling cascade, and modulate MDM2 function to regulate the p53-MDM2 interaction. We propose potential mechanisms by which nuclear PIP<sub>n</sub>s coordinate signaling with nuclear p53, AKT, and MDM2. Ultimately, we highlight that nuclear PIP<sub>n</sub>s serve as a ‘third messenger’ within the p53-MDM2 axis, expanding the current framework of non-canonical nuclear signaling in cancer biology. |
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| ISSN: | 2073-4409 |