ArticleNature cell biology2009
Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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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
155 citing papers in PubMed, 234 citations in OpenAlex.
- Guaianolide dimer KGA-1002 targets GRP94 and triggers unfolded protein response-associated degradation of SKP2/AKT axis as a novel antihepatoma agent.Journal of advanced research · 2026Article
- SKP2 Regulates Pulmonary Inflammatory Injury Triggered by Bacterial Infection Through p27-Mediated Degradation of FOXN3.MedComm · 2026Article
- FUCA2 Sustains AKT Signaling and Suppresses Senescence by Antagonizing FUT3-Mediated ErbB3 Fucosylation in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protist oxygen-sensing and the role of prolyl hydroxylase-regulation of E3(SCF) ubiquitin ligases.Biochimica et biophysica acta. General subjects · 2026Review
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Research Advances in Drug Resistance Mechanisms to Anti-HER2 Therapy in HER2-Positive Breast Cancer.Oncology research · 2026Review
- Docetaxel induced activation of GSDME pathway and pyroptosis enhance immune lethality in prostate cancer cells.Journal of experimental & clinical cancer research : CR · 2025Article
- LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of PD-L1 protein in non-small cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.Journal of virology · 2024Article
- Enzyme-independent role of EZH2 in regulating cell cycle progression via the SKP2-KIP/CIP pathway.Scientific reports · 2024Article
- O-GlcNAcylation of E3 ubiquitin ligase SKP2 promotes hepatocellular carcinoma proliferation.Oncogene · 2024Article
- Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.Cell death & disease · 2024Article
- MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Nature communications · 2023Article
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Role of Akt/Protein Kinase B in Cancer Metastasis.Biomedicines · 2023Review
- FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.Cell death & disease · 2023Article
- SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.Molecules and cells · 2023Article
- Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.Neoplasia (New York, N.Y.) · 2023Article
- Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.Frontiers in pharmacology · 2023Review
- SCF-SKP2 E3 ubiquitin ligase links mTORC1/ER stress/ISR with YAP activation in murine renal cystogenesis.The Journal of clinical investigation · 2022Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Skp2 is an F-box protein that forms the SCF complex with Skp1 and Cullin-1 to constitute an E3 ligase for ubiquitylation. Ubiquitylation and degradation of the p27 are critical for Skp2-mediated entry to the cell cycle, and overexpression and cytosolic accumulation of Skp2 have been clearly associated with tumorigenesis, although the functional significance of the latter is still unknown. Here we show that Akt/protein kinase B (PKB) interacts with and directly phosphorylates Skp2. We find that Skp2 phosphorylation by Akt triggers SCF complex formation and E3 ligase activity. A phosphorylation-defective Skp2 mutant is drastically impaired in its ability to promote cell proliferation and tumorigenesis. Furthermore, we show that Akt-mediated phosphorylation triggers 14-3-3beta-dependent Skp2 relocalization to the cytosol, and we attribute a specific role to cytosolic Skp2 in the positive regulation of cell migration. Finally, we demonstrate that high levels of activation of Akt correlate with the cytosolic accumulation of Skp2 in human cancer specimens. Our results therefore define a novel proto-oncogenic Akt/PKB-dependent signalling pathway.
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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.