ArticleOncogene2003
SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 102 citations in OpenAlex.
- RBL2 represses the transcriptional activity of Multicilin to inhibit multiciliogenesis.Cell death & disease · 2024Article
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Retinoblastoma Protein Is Required for Epstein-Barr Virus Replication in Differentiated Epithelia.Journal of virology · 2023Article
- CircRNA-Associated CeRNAs Regulatory Axes in Retinoblastoma: A Systematic Scoping Review.Frontiers in oncology · 2022Article
- Article
- Ubiquitin signaling in cell cycle control and tumorigenesis.Cell death and differentiation · 2021Review
- The Skp2 Pathway: A Critical Target for Cancer Therapy.Seminars in cancer biology · 2020Review
- The FBXL family of F-box proteins: variations on a theme.Open biology · 2020Article
- Regulation of cell cycle drivers by Cullin-RING ubiquitin ligases.Experimental & molecular medicine · 2020Review
- Mint3 depletion restricts tumor malignancy of pancreatic cancer cells by decreasing SKP2 expression via HIF-1.Oncogene · 2020Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
- A patent review of the ubiquitin ligase system: 2015-2018.Expert opinion on therapeutic patents · 2018Review
- RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines.Oncogene · 2018Article
- High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer.BMC cancer · 2018Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation.Molecular and cellular endocrinology · 2017Article
- Recent advances in SCF ubiquitin ligase complex: Clinical implications.Biochimica et biophysica acta · 2016Review
- Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins.The international journal of biochemistry & cell biology · 2016Review
- The Evolutionarily Conserved C-terminal Domains in the Mammalian Retinoblastoma Tumor Suppressor Family Serve as Dual Regulators of Protein Stability and Transcriptional Potency.The Journal of biological chemistry · 2015Article
- PP2A: more than a reset switch to activate pRB proteins during the cell cycle and in response to signaling cues.Cell cycle (Georgetown, Tex.) · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
p130 is a member of the retinoblastoma family of pocket proteins, which includes pRB and p107. Unlike pRB and p107, p130 protein levels decrease dramatically following its hyperphosphorylation starting in the mid-G1 phase of the cell cycle. However, the mechanism leading to p130 downregulation is unknown. We have found that the proteasome inhibitor, lactacystin, inhibited p130 downregulation in T98G cells progressing through the G1/S transition and S phase and that p130 is multiubiquitylated in 293 cells. We have previously shown that ectopic expression of both cyclin D and E induces phosphorylation and downregulation of p130. Since the SKP1/Cul1/SKP2 E3 ubiquitin ligase complex mediates ubiquitylation of substrates previously phosphorylated by cyclin-dependent kinases, we investigated the potential role of this ubiquitin ligase in mediating p130 downregulation. We found that p130 interacts with SKP1, Cul-1 and SKP2 in human 293 cells. We also found that ectopic coexpression of SKP2 and p130 leads to dose-dependent downregulation of p130, reduces p130 protein half-life and induces p130 ubiquitylation in these cells. Moreover, adenoviral-mediated expression of SKP2 accelerates downregulation of endogenous hyperphosphorylated p130 in mitogen-stimulated T98G cells and primary WI38 fibroblasts. We conclude that p130 is a substrate of the SCF(SKP2) ubiquitin ligase and this E3 ligase regulates p130 abundance during the cell cycle.
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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.