The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
A P53-Phosphoinositide Signalosome Regulates Nuclear AKT Activation
Open accessPublished version of a preprint
Abstract
The tumour suppressor p53 and PI3K-AKT pathways have fundamental roles in the regulation of cell growth and apoptosis, and are frequently mutated in cancer. Here, we show that genotoxic stress induces nuclear AKT activation through a p53-dependent mechanism that is distinct from the canonical membrane-localized PI3K-AKT pathway. Following genotoxic stress, a nuclear PI3K binds p53 in the non-membranous nucleoplasm to generate a complex of p53 and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3), which recruits AKT, PDK1 and mTORC2 to activate AKT and phosphorylate FOXO proteins, thereby inhibiting DNA damage-induced apoptosis. Wild-type p53 activates nuclear AKT in an on/off fashion following stress, whereas mutant p53 dose-dependently stimulates high basal AKT activity. The p53-PtdIns(3,4,5)P 3 complex is dephosphorylated to p53-phosphatidylinositol 4,5-bisphosphate by PTEN to inhibit AKT activation. The nuclear p53-phosphoinositide signalosome is distinct from the canonical membrane-localized pathway and insensitive to PI3K inhibitors currently in the clinic, which underscores its therapeutic relevance.
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“While years of research have primarily investigated AKT signaling at the cell membrane, recent works by Chen et al. [71] and Choi et al. [61] have revealed that, under genotoxic stress, IPMK-generated nuclear PIP3 binds to p53, which activates nuclear AKT signaling and suppresses apoptosis.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [71]
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Correlation Coefficients: Appropriate Use and Interpretation
Schober, P., Boer, C., & Schwarte, L. A. (2018) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000002864 · Cited by 10,986
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749
Alpelisib for PIK3CA -Mutated, Hormone Receptor–Positive Advanced Breast Cancer
André, F., Ciruelos, E., Rubovszky, G., Campone, M., Loibl, S., Rugo, H. S., Iwata, H., Conte, P., Mayer, I. A., Kaufman, B., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1813904 · Cited by 2,622
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906
Muller, P. A. J., & Vousden, K. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2641 · Cited by 1,647
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
Muller, P. A. J., & Vousden, K. H. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.021 · Cited by 1,545
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Jin, X., Ma, X., Xiang, Y., & Li, J. (2025) · Microchemical Journal · doi:10.1016/j.microc.2025.116584
Wu, Y., Chen, Z., Zheng, Z., Li, X., Shu, J., Mao, R., An, J., Fan, S., Luo, R., Guo, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26952322
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戴, 菲. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1652107
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Zhang, Y., & Wang, C. (2026) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbbio.2026.3713926
Ma, W., & Cai, H. (2026) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.71071
Bi, S., Wang, M., Guan, Q., Wang, Y., Liu, R., Zhang, J., Li, M., Liu, Q., Wang, P., Zhang, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-76647-5
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Metadata
- Authors
- Chen, M., Choi, S., Wen, T., Chen, C., Thapa, N., Lee, J. H., Cryns, V. L., & Anderson, R. A.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Cryns, Vincent L.
- Anderson, Richard A.
- Venue
- Nature Cell Biology
- Published
- 2022-07
- Volume
- 24
- Issue
- 7
- Pages
- 1099-1113
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC9833102
- OpenAlex
- W4284709570
- Cited by
- 117
- References
- 73
- Citations by year
- 2026: 20 · 2025: 44 · 2024: 27 · 2023: 18 · 2022: 7
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Cell Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (W81XWH-17-1-025, W81XWH-17-1-0259)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- p53, PI3K/Akt signaling, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 4,5-bisphosphate, PTEN, PDK1, mTORC2, genotoxic stress, DNA damage-induced apoptosis, tumour suppressor
- MeSH terms
- Cell Nucleus, Phosphatidylinositols, Tumor Suppressor Protein p53, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt
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