ArticleOncogene2015
Nuclear PRAS40 couples the Akt/mTORC1 signaling axis to the RPL11-HDM2-p53 nucleolar stress response pathway.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Postmenopausal Women.Cancer prevention research (Philadelphia, Pa.) · 2015Trial
- Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids: Phase II Pilot Study in Premenopausal Women.Cancer prevention research (Philadelphia, Pa.) · 2015Trial
- Leveraging Menstrual Effluent to Investigate Vitamin D and Human Decidualization: A Potential Link with Fertility.The Journal of clinical endocrinology and metabolism · 2026Article
- Integrative proteomics reveals MSH6 to modulate PARP inhibitor sensitivity in BRCA1/2-proficient ovarian cancer.PloS one · 2026Article
- tRF-21LeuTAA Promotes Oxidative Stress by Altering Glutathione Metabolic Enzymes to Support Prostate Cancer Progression.Cancer research · 2025Article
- Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders.PLoS computational biology · 2025Article
- Research Progress of Ribosomal Proteins in Reproductive Development.International journal of molecular sciences · 2024Review
- Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis.Reproductive biology and endocrinology : RB&E · 2024Article
- Cationic Liposomes Carrying HPV16 E6-siRNA Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells.Pharmaceutics · 2024Article
- Nuclear mTOR Signaling Orchestrates Transcriptional Programs Underlying Cellular Growth and Metabolism.Cells · 2024Review
- Spatial resolution of cellular senescence dynamics in human colorectal liver metastasis.Aging cell · 2023Article
- Article
- Rheb regulates nuclear mTORC1 activity independent of farnesylation.Cell chemical biology · 2022Article
- PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40.Cell death & disease · 2022Article
- P53 protein and the diseases in central nervous system.Frontiers in genetics · 2022Review
- p53 Inhibition Protects against Neuronal Ischemia/Reperfusion Injury by the p53/PRAS40/mTOR Pathway.Oxidative medicine and cellular longevity · 2021Article
- Location-specific inhibition of Akt reveals regulation of mTORC1 activity in the nucleus.Nature communications · 2020Article
- High PRAS40 mRNA expression and its role in prognosis of clear cell renal cell carcinoma.Translational andrology and urology · 2020Article
- Quantitative proteomic and phosphoproteomic profiling of ischemic myocardial stunning in swine.American journal of physiology. Heart and circulatory physiology · 2020Article
- PRAS40 hyperexpression promotes hepatocarcinogenesis.EBioMedicine · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The ribosomal protein (RP)-HDM2-p53 pathway has been shown to have key roles in oncogene-induced apoptosis and senescence, but the mechanism regulating this pathway remains elusive. The proline-rich Akt substrate of 40 kDa (PRAS40) has recently been identified as a binding partner and inhibitor of the mechanistic (formerly referred to as mammalian) target of rapamycin complex 1 (mTORC1). Although other inhibitors of mTORC1 are known tumor suppressors, PRAS40 promotes cell survival and tumorigenesis. Here we demonstrate that Akt- and mTORC1-mediated phosphorylation of PRAS40 at T246 and S221, respectively, promotes nuclear-specific association of PRAS40 with ribosomal protein L11 (RPL11). Importantly, silencing of PRAS40 induces upregulation of p53 in a manner dependent on RPL11. This effect is rescued by wild-type PRAS40, but not by the RPL11-binding-null PRAS40T246A mutant. We found that PRAS40 negatively regulates the RPL11-HDM2-p53 nucleolar stress response pathway and suppresses induction of p53-mediated cellular senescence. This work identifies nuclear PRAS40 as a dual-input signaling checkpoint that links cell growth and proliferation to inhibition of cellular senescence. These findings may help to explain the protumorigenic effect of PRAS40 and identify the PRAS40-RPL11 complex as a promising target for p53-restorative anticancer drug discovery.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.