ArticleCell2012
The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 254 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
254 citing papers in PubMed, 2 syntheses or guidelines pooled it, 461 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- 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
- Article
- Interactions Between E3 Ubiquitin Ligases and Deubiquitinases in AKT Regulation: Implications in Skeletal Muscle Homeostasis.Cell biochemistry and function · 2026Review
- The dinitrothiophenol SN-2 reduces osteoclastogenesis and estrogen deficiency-induced bone loss by inhibiting TRAF6 auto-ubiquitination.Bone reports · 2026Article
- Molecular Dynamics Simulation-Assisted siRNA Design for Dual-Ubiquitinated SKP2 Silencing via Ago2 Anchoring in Breast Cancer.ACS omega · 2026Article
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- PSMD14-mediated PFKFB2 deubiquitination activates H3K27 lactylation to drive cancer stemness in gastric adenocarcinoma.Cell death and differentiation · 2026Article
- PDIA6 promotes the cell proliferation of ESCC by enhancing the disulfide bond formation in TRAF4.Cellular & molecular biology letters · 2026Article
- Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression.Nature communications · 2026Article
- The Establishment of Prostate-specific, SKP2 Humanized Mice by CRISPR Knock-in Method Reveals Neoplastic Initiation and Microenvironmental Reprogramming.Research square · 2026Article
- 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
- Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.Current protein & peptide science · 2026Review
- Molecular dynamics simulations for understanding dual ubiquitination mechanisms to consider S-phase kinase-associated protein 2 (SKP2) as a potential drug target in breast cancer.Frontiers in chemistry · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- A pan-cancer analysis revealedPrecision clinical medicine · 2025Article
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
194 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Akt kinase plays a central role in cell growth, metabolism, and tumorigenesis. The TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and activation. Here, we show that Akt ubiquitination is also induced by activation of ErbB receptors; unexpectedly, and in contrast to IGF-1 induced activation, the Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated Akt ubiquitination and membrane recruitment in response to EGF. Skp2 deficiency impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and breast cancer progression in various tumor models. Moreover, Skp2 overexpression correlates with Akt activation and breast cancer metastasis and serves as a marker for poor prognosis in Her2-positive patients. Finally, Skp2 silencing sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests that distinct E3 ligases are utilized by diverse growth factors for Akt activation and that targeting glycolysis sensitizes Her2-positive tumors to Herceptin treatment.
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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.