ArticleThe Journal of biological chemistry2011
SKP2 oncogene is a direct MYC target gene and MYC down-regulates p27(KIP1) through SKP2 in human leukemia cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 95 citations in OpenAlex.
- Crotonylation impedes c-Myc oncogenic activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma.PloS one · 2026Article
- The tumor microenvironment enhances the expression of cssDNA by modulating cell cycle signaling pathways via SKP2.Scientific reports · 2025Article
- SKP2 regulates TERT independently of RUNX1/ETO in AML subtypes lacking the t(8,21) translocation via CDKN1B and RB phosphorylation states.Scientific reports · 2025Article
- PDCD11 Stabilizes C-MYC Oncoprotein by Hindering C-MYC-SKP2 Negative Feedback Loop to Facilitate Progression of p53-Mutant Breast and Colon Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.Aging and disease · 2024Review
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.Molecules and cells · 2023Article
- A RUNX1/ETO-SKP2-CDKN1B axis regulates expression of telomerase in t (8;21) acute myeloid leukemia.Cellular and molecular life sciences : CMLS · 2023Article
- MYC function and regulation in physiological perspective.Frontiers in cell and developmental biology · 2023Review
- ReducedCells · 2022Article
- MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding.Cancer research communications · 2022Article
- A Comprehensive Assessment of Genetic and Epigenetic Alterations Identifies Frequent Variations Impacting Six Prototypic SCF Complex Members.International journal of molecular sciences · 2021Article
- Stimulation of ROS Generation by Extract ofAntioxidants (Basel, Switzerland) · 2021Article
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- Gene Transactivation and Transrepression in MYC-Driven Cancers.International journal of molecular sciences · 2021Review
- p97/VCP is highly expressed in the stem-like cells of breast cancer and controls cancer stemness partly through the unfolded protein response.Cell death & disease · 2021Article
- Alternative approaches to target Myc for cancer treatment.Signal transduction and targeted therapy · 2021Review
- CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SKP2 is the ubiquitin ligase subunit that targets p27(KIP1) (p27) for degradation. SKP2 is induced in the G(1)-S transit of the cell cycle, is frequently overexpressed in human cancer, and displays transformation activity in experimental models. Here we show that MYC induces SKP2 expression at the mRNA and protein levels in human myeloid leukemia K562 cells with conditional MYC expression. Importantly, in these systems, induction of MYC did not activate cell proliferation, ruling out SKP2 up-regulation as a consequence of cell cycle entry. MYC-dependent SKP2 expression was also detected in other cell types such as lymphoid, fibroblastic, and epithelial cell lines. MYC induced SKP2 mRNA expression in the absence of protein synthesis and activated the SKP2 promoter in luciferase reporter assays. With chromatin immunoprecipitation assays, MYC was detected bound to a region of human SKP2 gene promoter that includes E-boxes. The K562 cell line derives from human chronic myeloid leukemia. In a cohort of chronic myeloid leukemia bone marrow samples, we found a correlation between MYC and SKP2 mRNA levels. Analysis of cancer expression databases also indicated a correlation between MYC and SKP2 expression in lymphoma. Finally, MYC-induced SKP2 expression resulted in a decrease in p27 protein in K562 cells. Moreover, silencing of SKP2 abrogated the MYC-mediated down-regulation of p27. Our data show that SKP2 is a direct MYC target gene and that MYC-mediated SKP2 induction leads to reduced p27 levels. The results suggest the induction of SKP2 oncogene as a new mechanism for MYC-dependent transformation.
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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.