ArticleBlood2008
Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 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.
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Who cites it
153 citing papers in PubMed, 265 citations in OpenAlex.
- Targeting tumor dormancy: the next frontier in gastrointestinal stromal tumor therapy.Neoplasia (New York, N.Y.) · 2026Review
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025Review
- Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.Scientific reports · 2025Article
- Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.Cell reports. Medicine · 2025Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Non-canonical deubiquitination of OTUB1 induces IFNγ-mediated cell cycle arrest via regulation of p27 stability.Oncogene · 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
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.Frontiers in oncology · 2024Review
- Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.Communications biology · 2023Article
- The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.Clinical and translational medicine · 2023Review
- Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers.Frontiers in immunology · 2023Review
- Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.Frontiers in pharmacology · 2023Review
- Functional roles of E3 ubiquitin ligases in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Review
- The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway.Cell death discovery · 2022Article
- The roles of E3 ligases in Hepatocellular carcinoma.American journal of cancer research · 2022Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Decreased p27(Kip1) levels are a poor prognostic factor in many malignancies, and can occur through up-regulation of SCF(Skp2) E3 ligase function, resulting in enhanced p27 ubiquitination and proteasome-mediated degradation. While proteasome inhibitors stabilize p27(Kip1), agents inhibiting SCF(Skp2) may represent more directly targeted drugs with the promise of enhanced efficacy and reduced toxicity. Using high-throughput screening, we identified Compound A (CpdA), which interfered with SCF(Skp2) ligase function in vitro, and induced specific accumulation of p21 and other SCF(Skp2) substrates in cells without activating a heat-shock protein response. CpdA prevented incorporation of Skp2 into the SCF(Skp2) ligase, and induced G(1)/S cell-cycle arrest as well as SCF(Skp2)- and p27-dependent cell killing. This programmed cell death was caspase-independent, and instead occurred through activation of autophagy. In models of multiple myeloma, CpdA overcame resistance to dexamethasone, doxorubicin, and melphalan, as well as to bortezomib, and also acted synergistically with this proteasome inhibitor. Importantly, CpdA was active against patient-derived plasma cells and both myeloid and lymphoblastoid leukemia blasts, and showed preferential activity against neoplastic cells while relatively sparing other marrow components. These findings provide a rational framework for further development of SCF(Skp2) inhibitors as a novel class of antitumor agents.
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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.