ArticleOncogene2013
PI3K regulation of the SKP-2/p27 axis through mTORC2.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- The lncRNA, CyKILRb acts as a ceRNA for tumor suppressive microRNA to augment oncogenic phenotype via induction of PIK3R2/PIMolecular therapy. Nucleic acids · 2026Article
- Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome.Endocrine · 2023Review
- The interplay between cell wall integrity and cell cycle progression in plants.Plant molecular biology · 2023Review
- Placental Remote Control of Fetal Metabolism: Trophoblast mTOR Signaling Regulates Liver IGFBP-1 Phosphorylation and IGF-1 Bioavailability.International journal of molecular sciences · 2023Article
- Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors.Signal transduction and targeted therapy · 2023Article
- Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer.Cancers · 2022Review
- Anticancer Activity of (±)-Kusunokinin Derivatives towards Cholangiocarcinoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Heparanase modulates the prognosis and development of BRAF V600E-mutant colorectal cancer by regulating AKT/p27Kip1/Cyclin E2 pathway.Oncogenesis · 2022Article
- Review
- Article
- An Unanticipated Modulation of Cyclin-Dependent Kinase Inhibitors: The Role of Long Non-Coding RNAs.Cells · 2022Review
- The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions.Cancers · 2021Review
- Article
- Elucidating the Molecular Basis of Sorafenib Resistance in HCC: Current Findings and Future Directions.Journal of hepatocellular carcinoma · 2021Review
- P27 Promotes TGF-Canadian respiratory journal · 2019Article
- mTORC2 regulates multiple aspects of NKT-cell development and function.European journal of immunology · 2017Article
- Regulation of mTORC1 by PI3K signaling.Trends in cell biology · 2015Review
- Point mutations of the mTOR-RHEB pathway in renal cell carcinoma.Oncotarget · 2015Article
- Celastrol induces cell cycle arrest by MicroRNA-21-mTOR-mediated inhibition p27 protein degradation in gastric cancer.Cancer cell international · 2015Article
- Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling.Journal of signal transduction · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The cyclin-dependent kinase inhibitor p27 is a key regulator of cell-cycle progression. Its expression and localization are altered in several types of malignancies, which has prognostic significance in cancers such as renal cell carcinoma (RCC). S-phase kinase-associated protein 2 (SKP-2) is an F-box protein that is part of the SKP-1/Cul1/F-box ubiquitin ligase complex that targets nuclear p27 among many other cell-cycle proteins for proteosomal degradation. Its overexpression has been observed in several tumor types. Signaling by phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) has previously been shown to regulate the SKP-2/p27 axis. Recent evidence suggests that PI3K signaling may activate mammalian target of rapamycin complex 2 (mTORC2) activity. As PI3K signaling is known to regulate SKP-2 and p27, we sought to determine whether these effects were mediated by mTORC2. Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity. We also demonstrate a novel role for mTORC2 in the modulation of nuclear p27 levels. In particular, mTORC2 signaling promotes the reduction of nuclear p27 protein levels through the increased protein expression of SKP-2. These are the first data to demonstrate a role for mTOR in the regulation of SKP-2. In concordance with these findings, mTORC2 activity promotes cell proliferation of RCC cells at the G1-S interphase of the cell cycle. Collectively, these data implicate mTORC2 signaling in the regulation of the SKP-2/p27 axis, a signaling node commonly altered in cancer.
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Registered trials
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.