ArticleBlood2012
F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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
59 citing papers in PubMed, 116 citations in OpenAlex.
- Targeted inhibition of FBXL2 confers susceptibility of HER2-negative breast cancer to trastuzumab deruxtecan.Nature cancer · 2026Article
- MicroRNAs as the critical regulators of ubiquitin-proteasome system through F-box protein targeting during tumor progression.Cancer cell international · 2025Review
- Low expression of MKRN1 promotes leukemia cell proliferation.European journal of medical research · 2025Article
- NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- FBXL6 is a vulnerability in AML and unmasks proteolytic cleavage as a major experimental pitfall in myeloid cells.Leukemia · 2024Article
- Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages.International journal of molecular sciences · 2024Article
- F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.International journal of medical sciences · 2024Review
- E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia.Journal of hematology & oncology · 2023Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The Prognostic Significance of theIndian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Fbxw11 impairs the repopulation capacity of hematopoietic stem/progenitor cells.Stem cell research & therapy · 2022Article
- Multi-Layered PLGA-PEI Nanoparticles Functionalized with TKD Peptide for Targeted Delivery of Pep5 to Breast Tumor Cells and Spheroids.International journal of nanomedicine · 2022Article
- The Long-Lost Ligase: CRL4DNA and cell biology · 2021Article
- FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.Nature communications · 2021Article
- Endotoxin stabilizes protein arginine methyltransferase 4 (PRMT4) protein triggering death of lung epithelia.Cell death & disease · 2021Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- CRL4Nature · 2021Article
- A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance.Nature chemical biology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G(0) phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G(0) phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCF(FBXL2) in lymphoproliferative malignancies.
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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.